Cases Of Hodgkin's Disease Research Articles

Deep-learning based classification of a tumor marker for prognosis on Hodgkin's disease.

Hodgkin's disease is a common malignant disorder in adolescent patients. Although most patients are cured, approximately 10%-15% of patients experience a relapse or have resistant disease. Furthermore, there are no definitive molecular predictors for early identification of patients at high risk of treatment failure to first line therapy. The aim of this study was to evaluate the deep learning-based classifier model of medical image classification to predict clinical outcome that may help in appropriate therapeutic decisions. Eighty-three FFPE biopsy specimens from patients with Hodgkin's disease were stratified according to the patient's qPET scores, stained with picrosirius red dye and digitalized by whole slide image scanning. The resulting whole slide images were cut into tiles and annotated by two classes based on the collagen fibers' degree of coloring with picrosirius red. The neural network (YOLOv4) was then trained with the annotated data. Training was performed with 30 cases. Prognostic power of the weakly stained picrosirius red fibers was evaluated with 53 cases. The same neural network was trained with MMP9 stained tissue slides from the same cases and the quantification results were compared with the variant from the picrosirius red cases. There was a weak monotonically increasing relationship by parametric ANOVA between the qPET groups and the percentages of weakly stained fibers (p = .0185). The qPET-positive cases showed an average of 18% of weakly stained fibers, and the qPET-negative cases 10%-14%. Detection performance showed an AUC of 0.79. Picrosirius red shows distinct associations as a prognostic metric candidate of disease progression in Hodgkin's disease cases using whole slide images but not sufficiently as a prognostic device.

Second Primary Malignancies and Cardiovascular Mortality in Hodgkin disease Survivors — a Surveillance, Epidemiology, and End Results Registry Database Study

BackgroundOver the last few decades there has been significant improvements in survival in patients with Hodgkin disease (HD). But long-term HD survivors, especially those treated with radiation therapy (RT) have an increased risk of second primary malignancy and cardiovascular disease (CVD) related mortality. In this context, we conducted this population based study to analyze trends in CVD related mortality and incidence of lung and thyroid cancer in HD survivors treated with RT.Materials and methodsWe used the Surveillance, Epidemiology, and End Results 9 database to calculate the Standardized Incidence Ratio (SIR) and Excess Absolute Risk (EAR) of lung and thyroid cancer as second primary malignancies in survivors of HD diagnosed between 1973 and 2011, and who were treated with RT. Poisson regression models were used to calculate adjusted incidence of lung and thyroid cancer. We further divided the patients diagnosed with HD during this period into two groups based on if or not they received RT and calculated the mortality due to CVD for each group, by year of diagnosis. Poisson regression models were used to calculate adjusted CVD mortality by year of HD diagnosis for each group. In all three cases, trends in incidence or mortality were evaluated by calculating the Estimated Annual Percentage Change (EAPC) from the regression coefficient for year of diagnosis.ResultsWe identified 11,916 HD cases that received RT from the SEER database, who were followed up for a median duration of 160 months (range - 12 to 480 months). Table 1 provides characteristics of the study population. 319 patients developed lung cancer (SIR of 3.72, 95% CI 3.32 - 4.15; EAR of 13.19 per 10,000 person years at risk) and 86 patients developed thyroid cancer (SIR of 3.67, 95% CI 2.94 - 4.53; EAR of 3.54 per 10,000 person years at risk). Median ages at diagnosis of secondary lung and thyroid cancers were 59 years and 42 years respectively, with median latency periods of 16 years and 17 years respectively. 965 patients among 11,916 patients who received RT died from CVD while the number of CVD deaths was 1,182 among the 12,507 patients who were not administered RT.Using Poisson regression models, we calculated the adjusted incidence of secondary lung cancer and thyroid cancer and the adjusted mortality from CVD, by year of diagnosis. Year of diagnosis, age at diagnosis of HD and latency (time since diagnosis of HD) were the independent variables used in the regression model. Between 1973 and 2011, the adjusted incidence of lung cancer declined at an EAPC of -2.68 (95% CI -13.06 to -3.92) and that of thyroid cancer declined at an EAPC of -3.35 (95% CI -5.73 to -1.00) (Figure 1). Over the same period, CVD mortality per 10,000 person years at risk for patients who received RT declined at an EAPC of -4.34 (95% CI -4.97 to -3.73) and that of patients who did not receive RT declined at an EAPC of -1.92 (95% CI -2.47 to -1.39) (Figure 2).ConclusionWe observed a decline in incidence of lung and thyroid malignancies and CVD mortality in HD survivors over the study period. The decline in CVD mortality over time in patients who received RT was steeper compared to that of patients who did not receive RT. Though our study was limited by the lack of details regarding RT, chemotherapy and comorbidities, these findings are most likely a reflection of recent trends in use of reduced doses and field of RT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Second Primary Malignancies and Cardiovascular Mortality in Hodgkin Disease (HD) Survivors – A SEER Database Study

Over the last few decades there has been significant improvements in survival in patients (pts) with HD. But long-term HD survivors, especially those treated with radiation therapy (RT) have an increased risk of second primary malignancy (SPM) and cardiovascular disease (CVD) related mortality. We conducted this population based study to analyze trends in CVD related mortality and incidence of lung and thyroid cancer (CA) in HD survivors treated with RT. We used the SEER 9 database to calculate the Standardized Incidence Ratio (SIR) and Excess Absolute Risk (EAR) of lung and thyroid CA as SPM in survivors of HD diagnosed between 1973 and 2011, who were treated with RT. Poisson regression models were used to calculate adjusted incidence of lung and thyroid CA. We also divided the pts diagnosed with HD during this period into two groups based on if or not they received RT and calculated the mortality due to CVD for each group, by year of diagnosis (YOD). Poisson regression models were used to calculate adjusted CVD mortality by YOD for each group. In all three cases, trends in incidence or mortality were evaluated by calculating the Estimated Annual Percentage Change (EAPC) from the regression coefficient for YOD. We identified 11,916 HD cases that received RT, who were followed up for a median duration of 160 months (range – 12 to 480 months). 319 pts developed lung CA (SIR of 3.72, 95% CI 3.32 – 4.15; EAR of 13.19 per 10,000 person years at risk (PYAR)) and 86 pts developed thyroid CA (SIR of 3.67, 95% CI 2.94 – 4.53; EAR of 3.54 per 10,000 PYAR). Median ages at diagnosis of secondary lung and thyroid CA were 59 yrs and 42 yrs, with median latency periods of 16 yrs and 17 yrs respectively. 965 pts among 11,916 pts who received RT died from CVD while the number of CVD deaths was 1,182 among the 12,507 pts who were not given RT. Using Poisson regression models, we calculated the adjusted incidence of secondary lung CA and thyroid CA and the adjusted mortality from CVD, by YOD. YOD, age at diagnosis of HD and latency (time since diagnosis of HD) were the independent variables used in the regression model. Between 1973 and 2011, the adjusted incidence of lung CA declined at an EAPC of -2.68 (95% CI -13.06 to -3.92) and that of thyroid CA declined at an EAPC of -3.35 (95% CI -5.73 to -1.00). Over the same period, CVD mortality per 10,000 PYAR for pts who received RT declined at an EAPC of -4.34 (95% CI -4.97 to -3.73) and that of pts who did not receive RT declined at an EAPC of -1.92 (95% CI -2.47 to -1.39). We observed a decline in incidence of lung and thyroid CA and CVD mortality in HD survivors over the study period. The decline in CVD mortality over time in pts who received RT was steeper compared to that of pts who did not receive RT. Though our study was limited by the lack of details regarding RT, chemotherapy and comorbidities, these findings are most likely a reflection of recent trends in use of reduced doses and field of RT.

A dose based approach for evaluation of inter-observer variations in target delineation.

Substantial inter-observer variations in target delineation have been presented previously. Target delineation for paediatric cases is difficult due to the small number of children, the variation in paediatric targets, the number of study protocols, and the individual patient's specific needs and demands. Uncertainties in target delineation might lead to under-dosage or over-dosage. The aim of this work is to apply the concept of a consensus volume and good quality treatment plans to visualise and quantify inter-observer target delineation variations in dosimetric terms in addition to conventional geometrically based volume concordance indices. Two paediatric cases were used to demonstrate the potential of adding dose metrics when evaluating target delineation diversity; Hodgkin's disease (case 1) and rhabdomyosarcoma of the parotid gland (case 2). The variability in target delineation (PTV delineations) between six centres was quantified using the generalised conformity index, CIgen, generated for volume overlap. The STAPLE algorithm, as implemented in CERR, was used for both cases to derive a consensus volumes. STAPLE is a probabilistic estimate of the true volume generated from all observers. Dose distributions created by each centre for the original target volumes were then applied to this consensus volume. A considerable variation in target segmentation was seen in both cases. For case 1 the variation was 374-960 cm3 (average 669 cm3) and for case 2; 65-126 cm3 (average 109 cm3). CIgen were 0.53 and 0.70, respectively. The DVHs in absolute volume displayed for the delineated target volume as well as for the consensus volume adds information on both "compliant" target volumes as well as outliers which are hidden with just the use of concordance indices. The DVHs in absolute volume add valuable and easily understood information to various indices for evaluating uniformity in target delineation.

Lower Leukocytosis with Biosimilar Compared with Originator G-CSF during Autologous Stem Cell Mobilization after Chemotherapy in Lymphoma and Multiple Myeloma Patients. a Pharmacovigilance Study of “Rete Ematologica Lombarda” (FARMA-REL)

BACKGROUNDBased on therapeutic equivalence extrapolated from originator, the use of biosimilar Granulocyte-Colony Stimulating Factor (G-CSF) in the context of stem cell harvest was approved by the European Medicines Agency (EMA), however “ad hoc” studies are limited. AIMSTo assess the efficacy and safety profile of biosimilar compared with originator G-CSF on PBSC autologous mobilization in association with chemotherapy (CT) in lymphoma (LY) and multiple myeloma (MM) patients (pts) treated in the Hematology Units of “Rete Ematologica Lombarda” (REL). PATIENTS AND METHODSData retrospectively collected from consecutive pts with Hodgkin disease (HD), non-Hodgkin LY (NHL) and MM undergoing PBSC harvest after CT with biosimilar filgrastim between July 2012 and December 2013 (LY) or June 2014 (MM), were compared with a historical control group treated with originator G-CSF. Biosimilar G-CSF was used at doses ranging from 5 (MM and lymphoma HIV-negative) to 10 mcg/kg/d (lymphoma HIV-positive) subcutaneously, starting from the day after the end of CT until the end of leukapheresis. The Shapiro-Wilk test was used to assess normality of data: p-values were derived from chi-square test for categorical data and from Mann–Whitney U-test for continuous data. RESULTSOne hundred-five leukapheresis from 96 consecutive pts including 3 HD, 51 NHL (46 HIV-negative and 5 HIV-positive) and 42 MM cases were analyzed. Median age was 53 yrs (19-65) among LY and 63 (43-72) among MM pts. Thirty-two/54 (59 %) and 19/42 (45 %) cases were male, respectively. Mobilization was planned as part of first line CT in 65% of LY pts; only one case was mobilized during 3rd line CT. Forty-five LY cases (47 %) had been previously treated with alkylating drugs (47 %), three (3 %) with fludarabine-containing regimens. All MM pts mobilized after first line CT.Mobilization started a median of 13 (range 10-21) and 10 (range 10-18) days after CT for LY and MM, respectively; it was completed in a median of one procedure (range: LY 1-4, MM 1-3). Median number of CD34+ cells collected was: 9,1 (range 3,0-47) and 7,8 (range 4,1-12,9) x 106/Kg/pt in LY and MM pts, respectively. Planned end-point was reached in all MM cases and all but 2 LY cases (3 %).Biosimilar G-CSF use was well tolerated in both LY and MM pts: mild bone pain (WHO grade 1-2) was frequently reported (LY: 16/54, 23 %; MM: 16/42, 38 %); two LY pts needed treatment with acetaminophen for headache (1) and bone pain (1), both WHO grade 3.Data were compared with a historical control group of 58 LY pts (HD 10, NHL 45, NHL-HIV 3) and 32 MM pts mobilized with originator G-CSF (filgrastim or lenograstim)(Table): while MM cohorts are similar, LY cohorts differed for a higher frequency of mobilization with high-dose cyclophosphamide (2/54, 4 % vs. 14/58, 24 %, p<0.001) and a slight prevalence of HD cases (3/54, 5 % vs. 10/58, 17%, p= 0.053) only. Median number of procedures, CD34+ count peak and CD34+ collected were similar in both groups; however a difference in median WBC count peak during leukapheresis was documented in both cohort, statistically significant in LY, even if treated without cyclophosphamide.CONCLUSION. We confirm efficacy and safety of biosimilar filgrastim for autologous PBSC mobilization in LY and MM pts. Noteworthy, biosimilar seems to be more selective on CD34+ cells compared with originator G-CSF, inducing efficient CD34+ cells mobilization with lower leukocytosis. This result, confirmed in both LY and MM populations, needs to be proved in larger studies and can play a major role in the setting of voluntary donors. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Value of 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography scan versus diagnostic contrast computed tomography in initial staging of pediatric patients with lymphoma

Our objective was to evaluate the value of 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) versus diagnostic contrast CT in the initial staging of pediatric Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL). Thirty patients with HD and 21 patients with NHL were included in this retrospective study. On nodal lesion analysis, PET/CT detected 94.8% (HD) and 88.3% (NHL) of total lesions, respectively, in contrast to 82.6% (HD) and 69.1% (NHL), respectively, for diagnostic contrast CT. PET/CT also detected more extranodal lesions. On the patient level, PET/CT detected additional lesions in 50% of patients with HD and in 42.9% of patients with NHL. In contrast, diagnostic contrast CT detected additional lesions in 16.7% (HD) and 23.8% (NHL) of total cases. FDG PET/CT led to upstaging in seven cases of HD and seven cases of NHL, while diagnostic contrast CT upstaged two cases of NHL. We conclude that FDG PET/CT outperforms diagnostic contrast CT in the initial staging of pediatric patients with lymphoma.

CANCER RISK FROM IN UTERO EXPOSURE TO CHERNOBYL FALLOUT IN UKRAINE

Background and Aims: - Iodine-131 (I-131), the major component of Chernobyl fallout and an isotope readily absorbed by the thyroid gland, has been clearly linked to a subsequent increase in thyroid cancer among those exposed in early childhood. The embryo/fetus could also be vulnerable given the small size of the gland, the proliferative activity of fetal thyroid cells, and the high rate of radioiodine accumulation from the maternal circulation after 12 weeks gestation. We evaluated risk of thyroid cancer from in utero exposure to I-131 and also explored the incidence of non-thyroid cancers. Methods: We identified 2,582 mother-child pairs from the northern region of Ukraine in which the mother was pregnant at the time of the Chernobyl accident or the two months following when I-131 fallout was still present. Individual fetal thyroid I-131 doses were estimated from I-131 activity in the mother’s thyroid (mean dose=72 mGy; range 0-3,230 mGy). From 2003-2006, the in utero cohort was screened using an in-depth, standardized clinical examination. To evaluate incidence of other cancers, we linked the cohort to the Ukrainian National Cancer Registry (UNCR) for the period 1997 (the earliest year for which electronic records were available throughout the study area) and 2008, and estimated the standardized incidence ratio (SIR). Results:Seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm were identified at the time of screening. The estimated excess odds ratio per Gray for thyroid carcinoma was markedly elevated (EOR/Gy=11.9) although not significantly so (P=0.12). Preliminary results of record linkage with the UNCR identified 6 cases of non-thyroid cancer, including 2 brain gliomas, 3 cases of Hodgkin disease, and 1 choriocarcinoma. The SIRs were 0.9 for males (95% confidence interval (CI): 0.11, 3.28) and 1.8 for females (95% CI: 0.49, 4.66). A subsequent linkage is currently underway. Conclusions : The data suggest that in utero exposure to I-131 in Ukraine may have increased the risk of thyroid carcinoma 20 years after the Chernobyl accident. Given the young age of the cohort, the results for cancer incidence at other sites are based on small numbers and should be interpreted cautiously.

Hodgkin disease risk: Role of genetic polymorphisms and gene–gene interactions in inflammation pathway genes

Inflammation is a critical component of cancer development. The clinical and pathological features of Hodgkin disease (HD) reflect an abnormal immunity that results from cytokines secreted by Reed-Sternberg cells and the surrounding tumor. Numerous studies have reported the association between genetic polymorphisms in cytokine genes and the susceptibility to different hematologic cancers. However, the effects of such SNPs on modulating HD risk have not yet been investigated. We hypothesized that gene-gene interactions between candidate genes in the anti- and pro-inflammatory pathways carrying suspicious polymorphisms may contribute to susceptibility to HD. To test this hypothesis, we conducted a study on 200 HD cases and 220 controls to assess associations between HD risk and 38 functional SNPs in inflammatory genes. We evaluated potential gene-gene interactions using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction, and classification and regression tree (CART) approaches. We observed that, in combination, allelic variants in the COX2, IL18, ILR4, and IL10 genes modify the risk for developing HD. Moreover, the cumulative genetic risk score (CGRS) revealed a significant trend where the risk for developing HD increases as the number of adverse alleles in the cytokine genes increase. These findings support the notion that epigenetic-interactions between these cytokines may influence pathogenesis of HD modulating the proliferation of regulatory T cells. In this way, the innate and adaptative immune responses may be altered and defy their usual functions in the host anti-tumor response. Our study is the first to report the association between polymorphisms in inflammation genes and HD susceptibility risk.

Avascular Necrosis of the Femoral Head in Patients with Hodgkin's Disease

Avascular necrosis of the femoral head (ANFH) is a rare complication that may occur in patients diagnosed with Hodgkin's Disease (HD), as a result of treatment. A review was made of 315 cases of HD treated with systemic chemotherapy associated with high doses of steroids and radiation therapy and 18 patients (5.71%) were found to have developed ANFH during treatment. The mean follow-up time for chemotherapy was 40 months (range 20-110 months) with an average dose of prednisone of 8.45 g (range 3.20 - 18.50). The patients were treated by simple forage, simple forage plus IES and total hip arthroplasty (THA). In 8 cases (44.44%) forage associated with IES was performed as the initial treatment option and 6 of these cases were found to be in Ficat stage II (75%), 1 was found to be in stage III (12.55%) and another in stage IV (12.5%). In 2 cases, the central decompression technique was used (Simple Forage); both were in Ficat stage II. In the other 8 cases, a total hip arthroplasty (THA) was chosen as the initial treatment option, with 3 of these patients in Ficat stage III and 5 in Ficat stage IV. The clinical outcomes (time to postoperative pain, time to radiological failure, and time to arthroplasty from the forage) following surgical management using the forage-biopsy technique with and without internal electrostimulation (IES) were recorded. We observed that treatment with Forage + IES was better than simple Forage in stages below III in patients with Hodgkin's Disease. We considered that in Ficat stage III and IV arthroplasty (THA) was the better option. Steroids do not appear to be the only factor that worsens the outcomes of the parameters tested, and, in our opinion, other associated factors exist.

Cardiac death 25 years after successful treatment for Hodgkin's disease—Case report

In the following case, the authors are discussing a connection between treating Hodgkin's disease in childhood and later sudden cardiac death of the patient at the age of 37. Examined expert literature describes injuries of the myocardium because of therapeutic irradiation in the childhood.

Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors

AbstractWe present results of peripheral blood stem cell (PBSC) mobilization, collection, and follow-up from 3928 consecutive unrelated stem cell donors. Assessments were performed prospectively at baseline, leukapheresis, 1 month, 6 months, and annually after PBSC donation. During follow-up, side effects were recorded by return post questionnaires. The median CD34+ cell counts on day 5 were 67.5/μL in male and 51/μL in female donors. Bone pain and headache were the most common side effects of recombinant human granulocyte-colony stimulating factor. Central venous access was required for 23 donations (0.6%). Throughout the follow-up, the absolute neutrophil counts were slightly below the initial baseline values but remained within the normal range. The majority of the donors reported good or very good health. Malignancies occurred in 12 donors (0.3%), among whom were 1 case of acute myeloid leukemia, 1 case of chronic lymphatic leukemia, and 2 cases of Hodgkin disease. Only the incidence of Hodgkin lymphoma differed significantly from an age-adjusted population. In conclusion, 7.5 μg/kg per day lenograstim proved to be safe and effective for mobilizing hematopoietic stem cells for allogeneic transplantation. Long-term monitoring of healthy PBSC donors remains important to guarantee the safety standards of PBSC mobilization and collection.

Hodgkin Disease With Spinal Cord Compression

Hodgkin disease is a nodal disease. Spinal cord or root compression is a rare complication and usually seen in the setting of progressive, advanced disease. We report 2 cases of Hodgkin disease in pediatric patients who presented with neurologic signs. One patient had paravertebral masses and involvement of thoracic vertebrae, which was initially misdiagnosed as spinal tuberculosis. The second patient who presented with paraplegia and bladder and bowel involvement had an epidural mass with collapse of thoracic vertebra. Lymph node biopsy revealed Hodgkin disease, mixed cellularity in both the cases. Both were treated with chemotherapy followed by radiotherapy.

A Rare Presentation of Central Nervous System in a Pediatric Patient With Hodgkin Disease

Intracranial involvement by Hodgkin disease is rare. We report a pediatric patient with Hodgkin disease who had intracranial disease at presentation. The patient was referred to our hospital with a suspicion of central nervous system tumor. Although the most common presenting feature of intracranial Hodgkin disease is cranial nerve palsy with brain parenchyma being the most common intracranial site of involvement, to our best knowledge no pediatric case of Hodgkin disease presented with isolated cavernous sinus syndrome reported. We report this rare case because of its unusual presentation, in which Hodgkin disease presented with cavernous sinus syndrome. Physicians should consider the probability of Hodgkin disease in children of all ages who present with cavernous sinus syndrome.

Autologous stem cell transplant in a patient with Down syndrome and relapsed Hodgkin lymphoma

Children with Down syndrome (DS) are at increased risk for the development of acute leukemia but they rarely develop other hematologic malignancies or solid tumors. Despite aggressive supportive care, DS patients have increased risk of treatment related morbidity and mortality compared to other children. There are few reported cases of Hodgkin disease in children with DS, and no reported cases of successful therapy for patients with relapsed disease. We report on a child with DS and relapsed Hodgkin disease who was successfully treated with high-dose chemotherapy and autologous stem cell transplant.

Genetic polymorphisms in DNA repair genes as modulators of Hodgkin disease risk

Although the pathogenesis of Hodgkin disease (HD) remains unknown, the results of epidemiologic studies suggest that heritable factors are important in terms of susceptibility. Polymorphisms in DNA repair genes may contribute to individual susceptibility for development of different cancers. However, to the authors' knowledge, few studies to date have investigated the role of such polymorphisms as risk factors for development of HD. The authors evaluated the relation between polymorphisms in 3 nucleotide excision repair pathway genes (XPD [Lys751Gln], XPC [Lys939Gln], and XPG [Asp1104His]), the base excision repair XRCC1 (Arg399Gln), and double-strand break repair XRCC3 (Thr241Met) in a population of 200 HD cases and 220 matched controls. Variants were investigated independently and in combination; odd ratios (OR) were calculated. A positive association was found for XRCC1 gene polymorphism Arg399Gln (OR, 1.77; 95% confidence interval [95% CI], 1.16-2.71) and risk of HD. The combined analysis demonstrated that XRCC1/XRCC3 and XRCC1/XPC polymorphisms were associated with a significant increase in HD risk. XRCC1 Arg/Arg and XRCC3 Thr/Met genotypes combined were associated with an OR of 2.38 (95% CI, 1.24-4.55). The XRCC1 Arg/Gln and XRCC3 Thr/Thr, Thr/Met, and Met/Met genotypes had ORs of 1.88 (95% CI, 1.02-4.10), 1.97 (95% CI, 1.05-3.73), and 4.13 (95% CI, 1.50-11.33), respectively. XRCC1 Gln/Gln and XRCC3 Thr/Thr variant led to a significant increase in risk, with ORs of 3.00 (95% CI, 1.15-7.80). Similarly, XRCC1 Arg/Gln together with XPC Lys/Lys was found to significantly increase the risk of HD (OR, 2.14; 95% CI, 1.09-4.23). These data suggest that genetic polymorphisms in DNA repair genes may modify the risk of HD, especially when interactions between the pathways are considered.

Vanishing Bile Duct Syndrome and Hodgkin Disease

This is the first description in which the diagnosis of vanishing bile duct syndrome (VBDS) preceded the diagnosis of Hodgkin disease (HD) by several months, and for which patients received modifications to modern MOPP-ABV chemotherapy with successful clinical remission. VBDS is an uncommon form of liver disease manifested by severe cholestasis and progressive liver failure. We report 2 cases of stage IIIB pediatric HD and VBDS. Because VBDS is progressive and the only curative treatment is liver transplant, it is imperative to recognize that children with VBDS may also have concurrent HD.

A 15-year-old girl with recurrent pneumonia

Hodgkin's disease (HD) represents a group of lymphomas with distinct clinical and histopathological features that account for approximately 5% of cancers in patients who are <15 years old and approximately 15% in patients who are 15-19 years old. Although the cause of HD is unknown, serologically confirmed infectious mononucleosis has been associated with an increased risk of HD, in addition to its known association with Burkitt's lymphoma. The Reed-Sternberg (RS) cell, a large and multinucleated cell with unique morphology, is the hallmark cell of HD. RS cells are clonal tumor cells that recently have been shown to be derived from B cells originating from germinal centers. Of four histological subtypes of HD, three have a good to excellent prognosis when recognized and treated early. We report a case of HD in a 15-year-old adolescent with a 14-month history of recurrent pneumonia. Open lung biopsy ultimately led to the diagnosis of HD. Although uncommon in this age group, the need to consider the possibility of neoplasm in the setting of recurrent respiratory infection is illustrated in this case. Early diagnosis and intervention may determine the prognosis of such neoplasms.

Biologic Features and Treatment Outcome of Secondary Acute Lymphoblastic Leukemia - Review of 101 Cases.

Secondary acute lymphoblastic leukemia (sALL) is a rare disease and its biologic features are not well described. Data suggested that sALL occurs more frequently at older age. Since leukemia at older age in general is associated with worse outcome, we wanted to assess the biology and outcome of patients with sALL by age at time of primary diagnosis. We describe a cohort of 7 patients and found additional 94 cases in the literature on whom biological parameters were described. Patients were stratified (at least 5 patients per strata) according to their age at initial diagnosis (<18, 18–59, and ≥60 years of age), initial diagnosis [acute myeloid leukemia (AML), Hodgkin's disease (HD), neuroblastoma, breast and prostate cancers], cytogenetic groups [diploid, t(9;22), 11q23 aberrations, complex karyotype], immunophenotypes (B vs. T), and Burkitt's defined by either morphology and/or cytogenetic analysis demonstrating c-myc rearrangement. A total of 101 patients were evaluated; 29 were <18, 54 were 18–59 and 18 were ≥60 years old. The distribution of primary diagnoses was as expected: neuroblastoma was seen only in the <18 age group (P=0.003), HD was more common in the 18–59 age group (75% of all HD cases; P=0.084) while breast (P=0.003) and prostate (P=0.005) cancers were prevalent only in the >18 year old patients. The time interval to develop sALL was similar among the three age groups (3, 2.2 and 1.8 years, P=0.561). However, the time interval to develop sALL was longer for HD (5.5 years) and neuroblastoma (3.7 years) as compared to AML (1 year), breast (1.6 years) and prostate (1.98 years) cancers (overall P=0.0003). Further, the time interval to develop sALL was significantly longer for patients with complex karyotype (5.3 years) as compared to all other aberrations [11q23 − 1.78; t(9;22) − 1.9; diploid − 1.98 years; overall P=0.0497]. Disease characteristics at diagnosis were as follows: T cell immunophenotype was more common in the <18 age group (P=0.016) and the presence of 11q23, t(9;22), complex and normal karyotypes was equally distributed among the three age groups (P=0.2, 0.073, 0.635 and 0.271 individually). Complete remission was infrequent in the ≥60 age group (22.22%) compared to the other groups (73.9% for <18 and 67.7% for 18–59; P=0.025). Even though only patients <60 years old were transplanted (33.3% for <18 and 19.4% for 18–59; P=0.102), the overall survival was poor in all age groups [probability of survival at 1 year for <18=0.222, 18–59=0.226 and ≥60=0.3 (P=0.7941)]. Primary diagnoses, cytogenetic subgroups and immunophenotype did not affect outcome. In summary, the time interval to develop sALL is significantly longer for HD, neuroblastoma and complex karyotype. However, sALL is associated with very poor outcome regardless of age and any of the biologic features. Therefore, identification of prognostic factors to prevent the occurrence of sALL is needed.

Sperm Cryopreservation: Recent and Marked Increase in Use for Testicular Cancer Compared With Hodgkin Disease

In a public network of sperm banks, time trends in use of sperm cryopreservation by men with testicular cancer (TC) and Hodgkin disease (HD) were assessed from 1990 to 2004. During this period, overall incidence of sperm cryopreservation rose from 1.08 to 3.06 per 100 000 person-years for TC and from 0.79 to 1.20 for HD. Modeling suggests that in 2010 the expected rate will reach 5.90 per 100 000 for TC, compared with 1.39 for HD. This increase in sperm cryopreservation for TC and HD is similar to increases observed in incidence of these 2 diseases in France and other European countries. Although TC and HD are rare malignancies, they are the most common cancers in adolescents and young men (Bray et al, 2002). Recent advances in chemotherapy and/or radiotherapy treatments have improved the longterm survival of patients with these diseases (5-year survival rate is approximately 90%). Nevertheless, the side effects of treatment, especially infertility (decrease of 30%), are still a major preoccupation for these young patients who often have not yet fathered children (Huyghe et al, 2004). Accordingly, sperm cryopreservation and sperm banking are now offered to these men before treatment to preserve their capacity to conceive naturally or through assisted reproduction techniques (Hallak et al, 1999; Magelssen et al, 2005). With this aim in mind, a unique public network of sperm banks (Centre d’Etude et de Conservation des Oeufs et du Sperme [CECOS]) was created in France in 1984, and 22 centers now cover the whole country. Sperm banks appear to be increasingly used for sperm donation and to offer the possibility of preserving sperm in the event of disease or surgical treatment, especially for men with HD and TC (Agarwal, 2000). The recent and marked increase of these diseases in most industrialized countries is a major concern (Parkin et al, 1997), drawing the attention of oncologists to the need for sperm cryopreservation. Although this option is still underutilized, it is now becoming a good and safe practice to safeguard future fertility (Chung et al, 2004). The aim of this study was to assess time trends in the use of sperm banking over the period of 1990 to 2004 by men with TC or HD.

The Pathology of Hodgkin's Disease: What's New?

From the viewpoint of the pathologist, there are three major issues concerning Hodgkin's disease (HD) that must be addressed. First is making the correct diagnosis; second is identifying any pathological features that may be of prognostic importance; and third is defining the identity of the neoplastic cell. Since Hodgkin's disease (HD) was first described, the origin of the Reed-Sternberg cell and the pathogenesis of HD have remained elusive. Recently developed techniques have allowed investigators to analyze the immunophenotype and genotype of Reed-Sternberg cells. The results of these studies include recognition that, in many cases, Reed-Sternberg cells are of lymphoid origin. Thus, although in most cases of HD the diagnosis is straightforward on routinely stained sections, the conceptual dividing line between HD and non-Hodgkin's lymphoma is not as sharp as it once seemed. Occasionally, there is difficulty in distinguishing between HD and non-Hodgkin's lymphoma. Nevertheless, fundamental differences in the clinical features, histology, immunophenotype, and genotype between non-Hodgkin's lymphoma and HD remain. The impact of histological features on prognosis are controversial, largely because of the excellent prognosis of most cases of HD.