Partial 7q Isochromosome in Bone Marrow Following Treatment of Hodgkin's Disease

We report on a 29-year-old female followed for relapsed Hodgkin's disease. She had been diagnosed with Hodgkin's disease at 20 years of age and had been treated with chemotherapy. She had been in remission for six years when she relapsed, at which time she received chemotherapy for bone marrow transplant (BMT). After failure of BMT, she received additional chemotherapies with growth factors and radiation treatment. A bone marrow biopsy showed moderate hypercellularity with erythroid hyperplasia, but the karyotype had an abnormal clone containing an isochromosome derived from a 7q22 deletion.     

The appearance of immature cell leukemias after radiologic and cytostatic intensive therapy of Hodgkin's lymphoma]

Among 106 patients with Hodgkin's lymphoma in stage IIIB and IVB treated from September 1969 to June 1977 by a working team for hematology and oncology at the clinic and outpatients clinic of the Medical School of Erfurt, there were two cases (=1.9%) showing a final transition to leukaemia with immature cells. A third neoplasia which had developed in a former field of irradiation was additionally observed in one patient. The various possibilities arising from an oncologic effect of ionizing rays and those substances having a cytostatic effect are discussed. After frequent reports on the occurrence of secondary tumours following intensive radiological and cytostatic therapy of advanced Hodgkin's lymphoma the enhanced risk of a secondary tumour being induced by this combined therapy cannot be excluded. Various conclusions are drawn from that by the authors.     

Cutaneous relapse in Hodgkin's disease: a case report

BACKGROUND: Skin involvement in Hodgkin's disease is rare, can be seen in advanced stages of the disease and indicates a poor prognosis. CASE: A young male presented with multiple nodular lesions on the chest wall and matted cervical lymph nodes. Aspiration smears from skin lesions showed atypical mononuclear cells with a prominent nucleolus, many lymphocytes and plasma cells. Smears from the lymph nodes showed classical Reed-Sternberg cells in a polymorphous background. The cytologic diagnosis of Hodgkin's lymphoma was entertained and later confirmed on skin biopsy. Past history revealed that the patient had been diagnosed with Hodgkin's disease and treated for it 2 years earlier, but had been lost to follow-up during treatment. CONCLUSION: Cutaneous Hodgkin's disease should always be considered in smears from skin lesions showing atypical mononuclear cells in a polymorphous background, even in the absence of a definitive clinical diagnosis at the time of presentation.     

Autoimmune diabetes mellitus, Hodgkin's disease and Graves' ophthalmopathy in a patient with 8.1 ancestral haplotype.

In this report, we describe the case of a 43-year-old woman affected by type 1 diabetes mellitus diagnosed 8 years before, who developed Graves' disease 2 years after chemotherapy and mantle radiotherapy treatment for Hodgkin's disease. Bilateral Graves' ophthalmopathy appeared four months before our observations. Intravenous methyl-prednisolone therapy was started, but was interrupted due to severe metabolic failure. Autoantibodies (anti-islet cells, anti-thyroid, thyroid-stimulating, non-organ-specific) were positive. Since the clinical picture suggested a genetic immunological ground predisposing to autoimmunity, we evaluated her HLA haplotype. Genomic typing of the patient permitted identification of the 8.1 ancestral haplotype, a Caucasoid haplotype unique in its association with many immunopathological diseases. Moreover, we also observed a haplotype unusual in Caucasians, trans DRB1*1101, DQA1*0103, DQB1*0603. To our knowledge, HLA-related genetic risk of developing thyroid autoimmunity after neck irradiation has never been studied. Although we cannot confirm a direct association between the 8.1 ancestral haplotype or DRB1*1101, DQA1*0103, DQB1*0603 and the diseases described, we suggest considering immunological parameters and HLA typing in candidate patients for mantle radiation therapy for Hodgkin's disease or other tumors. HLA haplotype determination could be useful in identifying the patients at raised risk of developing autoimmune diseases after irradiation, thus permitting a more appropriate follow-up schedule.     

Treatment failures and severe complications in children with Hodgkin's disease

Therapy failures and severe complications in the treatment of 46 children affected with Hodgkin's disease are reported. All children were treated with polychemotherapy (modified MVPP scheme) and radiotherapy (high voltage therapy X-ray 210 KV; involved field radiotherapy). 42 patients came into a complete remission, with a median of 58 months in 37 patients (10--97 months). 6 patients 14.3%) suffered from a recidive, 5 of them came into a second remission. Life-threatening infections appeared in 3 patients. After 9 MVPP cycles an encephalopathy appeared in 2 boys, one of them died. After local radiotherapy a severe laryngitis developed in two patients. An azoospermia existed in 6 adolescent boys examined.     

Chromosomal damage in sperm of patients surviving Hodgkin's disease following MOPP (nitrogen mustard,vincristine, procarbazine,and prednisone) therapy with and without radiotherapy

Following fusion with hamster eggs, human sperm chromosomes from six Hodgkin's disease patients were analyzed to determine the genotoxic effects of therapy. Each patient had received two to six cycles of MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone), with or without radiotherapy, from 3 to 20 years before the study. A total of 571 cells from the six patients were analyzed; 9.8% of the cells had structural aberrations, and 1.6% were hyperhaploid. Analysis of 5998 metaphases from a control group of 24 male donors revealed only 6.9% of cells with structural aberrations and 0.8% aneuploidy. The increase in hyperhaploidy in the patients was statistically significant. Thus, results of this study suggest that the MOPP regimen, with or without radiotherapy, is capable of causing chromosome abnormalities in the sperm of Hodgkin's disease patients.     

Lung cancer following therapy for Hodgkin's disease

We describe a patient in whom lung cancer developed several years after he had received combined-modality therapy for Hodgkin''s disease. The literature concerning second malignant diseases, particularly thoracic tumours, that occur following combined-modality therapy for cancer is reviewed. It is important to recognize these entities, because chest symptoms or findings on x-ray films may be misinterpreted as representing late recrudescence of the first neo-plastic disease.     

Secondary neoplasms in two children with Hodgkin's disease]

In two out of 59 children with Hodgkin's disease treated with MVPP regimen combined with local irradiation and followed up over 10 years the secondary neoplasms were detected, i.e. in 3.4% with persisting remission of the underlying disease. Chondrosarcoma was diagnosed in one patient in the field of irradiation (after 13 years). This patient died. In the second patient two different tumors (squamous epithelioma and fibrosarcoma) developed after 7 and 9 years following irradiation of two different areas. Actually, there are not any symptoms in this female patients (working). To decrease the incidence of these serious complications of Hodgkin's disease treatment regimens introduced by the Polish Pediatric Leukemia Study Group since 1988, the use of alkylating agents in limited, and the dose of local irradiation is decreased.     

Breast reconstruction using tissue expanders and implants in Hodgkin's patients with prior mantle irradiation.

Women treated for Hodgkin's disease with mantle irradiation have an increased risk for developing breast cancer. Typically, breast malignancy in Hodgkin's patients presents bilaterally in a younger age group. Skin flap ischemia, poor skin expansion, implant extrusion, capsular contracture, and poor cosmesis are common sequelae of tissue expander/implant breast reconstruction after breast irradiation for failed breast conservation therapy. This has led most surgeons to favor autologous tissue reconstruction in this setting. This study was performed to determine the efficacy of tissue expander/implant breast reconstruction in breast cancer patients who have been treated with prior mantle irradiation for Hodgkin's disease. A retrospective analysis of all breast cancer patients with a history of Hodgkin's disease and mantle irradiation treated with mastectomy and tissue expander/implant reconstruction between 1992 and 1999 was performed. There were seven patients, with a mean age of 35 years (range, 28 to 42 years). The average interval between mantle irradiation and breast cancer diagnosis was 16 years (range, 12 to 23 years). All patients underwent two-stage reconstruction. Textured surface tissue expanders were placed in a complete submuscular position at the time of mastectomy. Expansion was initiated 2 weeks after insertion and continued on a weekly basis until completion. Expanders were replaced with textured surface saline-filled implants as a second stage. Patients were evaluated for skin flap ischemia, infection, quality of skin expansion, implant extrusion, capsular contracture, rippling, symmetry, and final aesthetic outcome. Breast cancer was bilateral in five patients and unilateral in two. Two patients did not undergo simultaneous bilateral breast reconstruction because of metachronous cancer development. One of the patients had an initial transverse rectus abdominis muscle flap breast reconstruction, followed by a tissue expander/implant reconstruction of the opposite breast. The average follow-up was 3 years. Complications were limited to one case of cellulitis after implant placement that resolved with intravenous antibiotics. There were no cases of skin flap ischemia, poor skin expansion, or implant extrusion. Overall patient satisfaction was high and revisions were not requested or required. Symmetry was best achieved with bilateral implants. This study demonstrates the efficacy of tissue expander/implant breast reconstruction in patients treated with prior mantle irradiation. In this series, tissue expansion was reliable with low morbidity. Second-stage placement of permanent implants yielded good aesthetic results without significant capsular contracture. Mantle irradiation did not appear to compromise the prosthetic breast reconstruction. Tissue expander/implant breast reconstruction should remain a viable option in this category of irradiated patients.     

Bronchoalveolar lavage in the assessment of pulmonary Hodgkin's disease

Abnormal chest radiographs in patients with Hodgkin's disease are occasionally due to pulmonary Hodgkin's disease. The fluids recovered from bronchoalveolar lavages (BALs) from 50 patients prior to autologous bone marrow transplantation for advanced Hodgkin's disease were examined. Abnormal chest roentgenograms were present in 24 patients (48%); 4 (17%) of these had Reed-Sternberg cells or their mononucleated variants in the lavage fluid and an alveolar lymphocytosis averaging 31.4% (normal: 11.5%). The lymphocytes were small and monotonous. Of the 20 patients with abnormal chest roentgenograms but no Reed-Sternberg cells in the lavage fluid, the lymphocyte count was 10.88%, with only 3 patients exceeding 17%. Two patients with normal chest roentgenograms had Reed-Sternberg-like cells in their lavage fluids and averaged 23% lymphocytes in their lavage differential count. Eosinophils averaged 1% or less of the lavage differential and were not predictive of pulmonary Hodgkin's disease. This experience suggests that pulmonary Hodgkin's disease can be diagnosed by BAL. Reed-Sternberg cells and their mononucleated variants can be recognized by their characteristic cytomorphologic features, although care must be taken not to misinterpret reactive binucleated macrophages as neoplastic cells. In patients with Hodgkin's disease, Reed-Sternberg cells should be sought when an alveolar lymphocytosis is present.     

Treating Hodgkin's disease: for whom the more means better?

During the last half century, our knowledge and expertise increased, and Hodgkin's disease became one of the most curable malignant diseases. However, our results are still not satisfactory in the case of advanced stage. Apart from standard chemotherapy regimens, several other, so-called intensive first line therapy schedules have been tried, whose common characteristic is that more antineoplastic drugs within a reasonably shorter period and sometimes with increased dose had been administered. Out of these regimens, escalated dose BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisolone), the therapy yielding the best results and inciting hot debates in the literature is discussed here in detail. Though many questions related to BEACOPP scheme are still unanswered and at present it is not recommended for use in first line therapy except for trials, it seems that patients under 60 years of age, with advanced stage disease having poor prognosis, may benefit from this treatment.     

A life-threatening multilocalized hidradenitis suppurativa case

The patient was a 38-year-old man. He had been suffering from hidradenitis suppurativa (HS) for approximately 20 years. He had active lesions at both axillas, hip, scrotum, and perineum, and inactive lesions located behind the ears, lower abdomen, and posterior neck. He was monitored and treated at different branches; he continuously used antibiotics and was given steroids at times. Antibiotic resistance developed subsequently. His general situation was bad; vital signs were poor; and he was in a state of sepsis and preshock, so this case was regarded as life-threatening. Total excision was performed first on the lesion at the right axilla, then on the lesion at the left axilla, and the parascapular fasciocutaneous flap was reversed. A skin graft was applied to the triangular defect on the scapula. No relapse occurred. Then the lesions at the hip were managed. Broad excision was used twice with the patient under general anesthesia; because the lesions spread to the retrococcygeal and gluteal muscles, coccyx resection and partial gluteal muscle resection were implemented. The defect was eliminated with a progressive flap. At the intergluteal sulcus, small lesions emerging at the median line were debrided with the patient under local anesthesia, and together with secondary recovery, the disease was completely managed. Lesions at the perineum and scrotum and at both inguinal areas were broadly excised and grafted. No lesion has relapsed so far. One year later, Hodgkin's lymphoma was diagnosed, and the patient was treated with chemoradiotherapy easily, because there was no infective focus. The disease is in remission now. The patient weighs 110 kg, is healthy, and is working again.     

Wilson's disease: a common liver disorder?

In two sibships 7 of 24 siblings were homozygous for Wilson''s disease. In family A, the largest kindred of this recessively inherited disease thus far reported, the proband presented with chronic active hepatitis, one sibling died of cirrhosis, a second had clinical evidence of chronic liver disease and two others had biochemical and histologic changes in liver biopsy specimens. In family B the proband had cirrhosis and portal hypertension and one sibling had biochemical and histologic evidence of liver disease. All six living patients had low serum concentrations of ceruloplasmin and copper and a high 24-hour urinary excretion of copper, which was greatly increased by administration of D-penicillamine. None showed neurologic abnormalities and only one had Kayser-Fleischer rings (detectable only by slit-lamp examination). Each patient had an erythrocyte sedimentation rate (ESR) of 8 mm/h or less. After 3 and 2 years, respectively, of D-penicillamine therapy the conditions of the two probands had improved. Liver function became normal in three siblings, and no abnormalities developed in the remaining one. Thus, since Wilson''s disease may present with chronic active hepatitis or cirrhosis with a normal ESR and without ocular or neurologic signs, it may be a more common cause of liver disease in young people than has been appreciated.     

Heart Failure in Hypophosphatemic Rickets: Complications from High-Dose Phosphate Therapy

ObjectiveTo report a rare case of hypophosphatemic rickets (HR) leading to extensive cardiac complications.MethodsWe present the clinical course and autopsy findings of a patient with HR, treated with chronic phosphate-only therapy as a child, who subsequently developed tertiary hyperparathyroidism leading to extensive cardiac calcifications and complications. We also review the literature on the pathophysiology of calcifications from HR.ResultsA 34-year-old man was diagnosed with HR at 4 years of age after presenting with growth delay and leg bowing. Family history was negative for the disease. He was initiated on high-dose phosphate therapy (2-6 g of elemental phosphorus/day) with sporadic calcitriol use between 4-18 years of age. For 6 years he received phosphate-only therapy. Subsequently, he developed nephrocalcinosis, heart valve calcifications, severe calcific coronary artery disease, heart block, and congestive heart failure. At a young age, he required an aortic valve replacement and a biventricular pacemaker that was subsequently upgraded to an implantable cardioverter defibrillator. Autopsy showed extensive endocardial, myocardial, and coronary artery calcifications.ConclusionCardiac calcification is a known sequela of tertiary hyperparathyroidism when it occurs in patients with renal failure, but it is rarely seen in HR due to high phosphate therapy. Phosphate alone should never be used to treat HR; high doses, even with calcitriol, should be avoided. It is important to be cognizant of high-dose phosphate effects and to consider parathyroidectomy for autonomous function, if needed. This case emphasizes the importance of appropriate therapy, monitoring, and management of patients with HR. (Endocr Pract. 2013;19:e8-e11)     

A giant pseudoaneurysm becoming apparent after cardiac resynchronisation therapy

A 57-year-old male patient with coronary artery disease developed a pseudoaneurysm after an inferior infarct in 1997. He underwent coronary bypass surgery and resection of the pseudoaneurysm located at the inferior wall. Unfortunately, the pseudoaneurysm recurred due to dehiscence of the patch, necessitating a second surgical intervention. After six years he developed progressive heart failure due to severe left ventricular dysfunction. He was referred to our institution for cardiac resynchronisation therapy (CRT) because of drug refractory heart failure which was associated with a left bundle branch block, ejection fraction of 12%, and a NYHA class IV status. After successful implantation of a biventricular pacemaker, a remarkable clinical recovery was observed. Left ventricular function improved and echocardiography now demonstrated that the pseudoaneurysm at the inferior wall had recurred for the third time. This diagnosis could not be established by preoperative echocardiography.     

Disorders in the menstrual cycle and fertility of women with Hodgkin's disease]

Sixty two women with Hodgkin's disease were questioned about disorders in their menstrual cycle and fertility. Menstrual cycle disorders were noted by 38 respondents, i.e. over 60%. Amenorrhoea persisted in 24 of these women. These disorders were significantly more frequent in patient over 30 year of age. There were 52 labours in the group of 38 women with menstrual cycle disorders prior to them, and 21 labours in a group of 24 women without any abnormalities. Hodgkin's disease was diagnosed in 6 patients during pregnancy: 2 of them were treated with irradiations on the upper part of the body while 4 remained untreated. After radiotherapy, there were 2 deliveries in women of the group with menstrual cycle disorders, and 9 deliveries in women without such disturbances. Answers to the supplied questionnaire did not provide any information on the congenital abnormalities in neonates.     

Treatment of persistent knee effusions with intra-articular radioactive gold.

Patients with a total of 112 chronic knee effusions unresponsive to the usual conservative methods of therapy were treated with intra-articular injections of radioactive gold and followed from 6 months to 5 years. Most patients in the study had rheumatoid arthritis but others had ankylosing spondylitis, psoriatic arthritis, intermittent hydrathrosis and undiagnosed synovitis. After 6 months 81% showed improvement. This figure diminished to approximately 70% at 1 and 2 years, 60% at 3 and 4 years and 50% at 5 years. The mose beneficial results were seen in patients with intermittent hydrarthrosis. Twelve patients with a synovial cyst and/or rupture improved. Patients with thin synovia and anatomic stage I or II disease did best, but those with stage III disease also did well. After the injection 33% of the patients had a reactive synovitis. A variable amount of radioactive material escaped from the knee to the regional lymph nodes and general circulation.     

Urinary neopterin in malignant lymphoma.

Urinary neopterin levels were studied in 96 patients with malignant lymphomas. Twenty-eight had Hodgkin's disease and 68 non-Hodgkin's lymphoma. Neopterin excretion was significantly related to the clinical stage of the disease. Mean neopterin excretion in patients with active disease (634 +/- 527 mumol neopterin/mol creatinine) was significantly higher (p = 0.000) than in patients in complete remission (198 +/- 105 mumol neopterin/mol creatinine). Mean neopterin levels of patients in stage III-IV were higher than for patients in stage I-II. These findings were the same in patients with Hodgkin's disease and those with non-Hodgkin's lymphoma (659 +/- 593-425 +/- 316 mumol neopterin/mol creatinine), regardless of the histological subtype. A significant correlation was found between neopterin excretion, ESR (r = 0.31; p = 0.003) and hemoglobin (r = -0.40; p = 0.000). Longitudinal analysis showed a trend towards a correlation between response to therapy and neopterin excretion. These findings suggest that neopterin may be a useful prognostic marker in non-Hodgkin's lymphoma.     

Hypothyroidism in Hodgkin's disease patients

PURPOSE: Study of thyroid function in Hodgkin's disease patients in complete remission. PATIENTS AND METHODS: We examined the thyroid function of 160 Hodgkin's disease patients in complete remission for at least one year, and determined the values of supersensitive thyroid stimulating hormone (sTSH), free T4 (fT4), free T3 (fT3) hormones. RESULTS: Normal values were observed in 117 patients, subclinical change (only elevated sTSH) in 28 patients, clinical hypothyroidism in 14 patients (also low fT4 and/or fT3), hyperthyroidism (Basedow's disease) in one patient. Hypothyroidism was one and a half times more frequent in females than in males. The normal and low thyroid function group did not differ from each other in mean age, histological subtypes, disease stage, general symptoms, and whether lymphangiography was performed. Hypothyroidism was more frequent in patients who had undergone mantle or neck radiotherapy. The onset of thyroid gland underfunction was more pronounced from six years after neck radiotherapy. The thyroid disease could be controlled using a daily dose of 25-225 mg levothyroxin. CONCLUSIONS: During the care of Hodgkin's disease patients routine examination of the thyroid function is important for the early recognition and prevention of treatment related late complications. On the other hand in treatment planning phase more attention should be paid to thyroid gland protection when neck radiotherapy is used.     

No evidence for prolonged excretion of polioviruses in persons with residual paralytic poliomyelitis in Ethiopia, Pakistan and Guatemala.

Persons who have developed acute flaccid paralysis following infection with wild-type polioviruses or vaccine-associated paralytic poliomyelitis usually excrete polioviruses for only a few weeks. However, some patients with paralytic poliomyelitis have had prolonged excretion of polioviruses for periods of up to 10 years after onset of disease. Most prolonged excretors have been identified in industrialized countries. We studied 348 patients 2-28 years old in Ethiopia, Pakistan and Guatemala with residual paralytic poliomyelitis to determine if they had IgA or IgG deficiency or persistent poliomyelitis excretion at least 1 year after onset of disease. None of the 348 affected individuals had IgG deficiency or persistent poliovirus excretion. One child had borderline low serum IgA concentration. Since we did not study children under 2 years of age, persons born with IgG deficiency disorders may have died in developing countries where replacement immunoglobulin therapy is not readily available. Nevertheless, persistent poliovirus excretion among persons 2 years of age and older with residual paralytic poliomyelitis is uncommon in developing countries.