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Hodgkin's Lymphoma

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Childhood Hodgkin's Lymphoma

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  • PubMed search for publications about Hodgkin Lymphoma - Limit search to: [Reviews]

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    MeSH term: Hodgkin Disease
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Pervez S, Abro B, Shahbaz H
Small lymphocytic lymphoma with Reed Sternberg cells: a diagnostic dilemma.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications
Reed Sternberg (RS) cells in the setting of small lymphocytic lymphoma (SLL) can complicate the histopathological diagnosis. We report a case of a man aged 54 years who presented with cervical lymphadenopathy. Resection of the lymph node was performed and sent for histopathological evaluation to a local laboratory. A diagnosis of SLL with Classic Hodgkin's lymphoma (CHL) was made. The medical oncologist who encountered this diagnosis for the first time sent the biopsy blocks to our laboratory for a second opinion. On review of the biopsy and immunohistochemical stains, it showed typical SLL morphology and immunophenotype. Focally, it showed large mononuclear RS type cells; however, no typical background of CHL was seen. The diagnosis was revised to 'SLL with RS like cells with no convincing evidence of CHL'. The patient was subsequently treated as a case of SLL and no progression was observed on a follow-up of 5 years.

Ferrari C, Niccoli Asabella A, Merenda N, et al.
Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment.
Medicine (Baltimore). 2017; 96(5):e5973 [PubMed] Free Access to Full Article Related Publications
We investigated the prognostic value of interim F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis.Thirty pHL patients (age ≤16) underwent serial F-FDG PET/CT: at baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (ΔΣSUVmax0-2, ΔΣSUVmean0-2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3-78).Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan-Meier method.Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for ΔΣSUVmax0-2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between ΔΣSUVmax0-2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P = 0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P = 0.005).Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (ΔΣSUVmax0-2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies.

Cho BB, Kelting SM, Gru AA, et al.
Cyclin D1 expression and polysomy in lymphocyte-predominant cells of nodular lymphocyte-predominant Hodgkin lymphoma.
Ann Diagn Pathol. 2017; 26:10-15 [PubMed] Related Publications
Cyclin D1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. Although increasingly recognized in other lymphoproliferative disorders, cyclin D1 expression and CCND1 gene abnormalities have not been well studied in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Using a double stain for CD20/cyclin D1, we quantified cyclin D1 expression in 10 cases of NLPHL and correlated those findings with SOX11 expression, CCND1 gene abnormalities, and clinical data. For comparison, we examined 5 cases of T cell-/histiocyte-rich large B-cell lymphoma (THRLBCL). All cases of NLPHL stained for cyclin D1 showed at least rare positivity in lymphocyte-predominant (LP) cells. In 4 cases, at least 20% of LP cells were positive for CD20/cyclin D1. Neither SOX11 expression nor CCND1 gene rearrangement was found in any of the cases, but fluorescence in situ hybridization showed a proportion of the large cells with 3 to 4 copies of nonfused IGH and CCND1 signals or 3 intact CCND1 break-apart signals. Further study with CCND1/CEP11 showed polysomy in 6 of 9 cases with cyclin D1 expression and 5 of 16 NLPHL not examined for cyclin D1. Two of 5 cases of THRLBCL showed rare positive staining for CD20/cyclin D1; 1 case showed polysomy with CCND1/CEP11. Results show that cyclin D1 may be expressed in LP cells without SOX11 expression or CCND1 translocation. Polysomy with increased copies of CCND1 may account for cyclin D1 expression in some cases. Cyclin D1 expression is not useful for distinguishing NLPHL from THRLBCL and has no apparent clinical significance in NLPHL.

Dubreuil J, Dony A, Salles G, et al.
Cat-Scratch Disease: A Pitfall for Lymphoma Evaluation by FDG-PET/CT.
Clin Nucl Med. 2017; 42(2):106-107 [PubMed] Related Publications
FDG-PET/CT is a standard of care in staging and response assessment of Hodgkin lymphoma. Hence, it is important to recognize pitfalls owing to the potential therapeutic impact. We report a case of a 29-year-old woman affected by stage III bulky Hodgkin lymphoma. The interim FDG-PET/CT showed a complete metabolic response. After three new cycles of chemotherapy, the patient showed fever and lymphadenopathy at clinic examination, PET/CT revealed several FDG uptakes at lymph nodes in inguinal and iliac region. Pathologic analyses, after biopsy and serologic examinations, led to the diagnosis of cat-scratch disease.

Das DK, Sheikh ZA, Al-Shama'a MH, et al.
A case of composite classical and nodular lymphocyte predominant Hodgkin lymphoma with progression to diffuse large B-cell non-Hodgkin lymphoma: Diagnostic difficulty in fine-needle aspiration cytology.
Diagn Cytopathol. 2017; 45(3):262-266 [PubMed] Related Publications
A small percentage of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) progresses to diffuse large B-cell lymphoma (DLBCL). There have also been rare reports of gray zone lymphoma with features intermediate between classical Hodgkin lymphoma (CHL) and DLBCL. We report a very rare case of composite lymphoma (CHL and NLPHL) progressing to DLBCL, and highlight the diagnostic difficulty faced during its fine-needle aspiration (FNA) cytology diagnosis. A 65-year-old woman presented with a right axillary swelling which was subjected to FNA cytology. The routine FNA cytology diagnosis was anaplastic large cell lymphoma (ALCL) but immunocytochemistry did not support this diagnosis completely. The histopathological diagnosis of the excised lymph node was NLPHL with progression to DLBCL in our hospital but in a hospital abroad where the patient was treated, the reviewed diagnosis was CHL. The patient had a rapid downhill course with development of terminal pleural effusion and died approximately one year from initial diagnosis.The review of the cyto-histologic material along with additional immunocyto/histochemical studies and the clinical course of the disease support the diagnosis of a composite lymphoma (CHL and NLPHL) with progression to DLBCL. It is suggested that all the three lesions were clonally related. Diagn. Cytopathol. 2017;45:262-266. © 2016 Wiley Periodicals, Inc.

Sathyanarayanan V, Hagemeister F
Targeted therapies for Hodgkin lymphoma: results of recent trials.
Rinsho Ketsueki. 2016; 57(10):2049-2053 [PubMed] Related Publications
Many patients with Hodgkin lymphoma (HL) can be cured with standard chemotherapy with high long term survival rates(1)). Considering the increased risks of various toxicities following therapy, options are evolving towards avoidance of radiation and reduction of therapy duration, with results similar to those currently achieved with improved quality of life(2, 3)). However, 20-30% of patients still develop recurrence during or following initial therapy, depending upon what chemotherapy regimen is administered(4)). Investigators have recently described new agents that have produced significant responses in this latter group of patients. In this report, we describe some of these studies, with an emphasis on response and tolerability.

Terauchi T
Update on the use of FDG-PET/CT in malignant lymphoma.
Rinsho Ketsueki. 2016; 57(10):2008-2012 [PubMed] Related Publications
This article aims to explain the current status of FDG-PET/CT in malignant lymphoma management by reviewing the new recommendations for evaluation, staging, and response assessment in patients with malignant lymphoma, published as the Lugano Classification in 2014. FDG-PET/CT was formally incorporated into standard staging for FDG-avid lymphoma in this new classification. Nearly all subtypes of malignant lymphoma are FDG-avid. In staging, the increased FDG uptake compatible with lymphoma is considered to represent involvement of lymphoma, regardless of size, and the FDG-avid lesion is potentially a good biopsy target. FDG-PET/CT is more sensitive than bone marrow biopsy in diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). Location, size and FDG uptake, based on a 5 point scale (compared to hepatic uptake and mediastinal blood pool) for the residual lesion, constitute useful information for response assessment. Routine surveillance scans after remission are discouraged, especially for DLBCL and HL. Interim PET is regarded as a promising biomarker for stratifying treatments of malignant lymphoma, although its usefulness remains controversial.

Gharbaran R
Insights into the molecular roles of heparan sulfate proteoglycans (HSPGs-syndecans) in autocrine and paracrine growth factor signaling in the pathogenesis of Hodgkin's lymphoma.
Tumour Biol. 2016; 37(9):11573-11588 [PubMed] Related Publications
Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there is very limited data for this interaction in cHL. Thus, this review highlights the relevant literature focusing on the potential interactions of SDCs and GFs in cHL pathogenesis. Also discussed are the pre-clinical and clinical studies targeting signaling through these pathways.

Martínez C, Jorge AS, Pereira A, et al.
Comorbidities, not age, are predictive of survival after autologous hematopoietic cell transplantation for relapsed/refractory Hodgkin's lymphoma in patients older than 50 years.
Ann Hematol. 2017; 96(1):9-16 [PubMed] Related Publications
Autologous hematopoietic cell transplantation (AHCT) is the standard of care for young patients with relapsed/refractory (R/R) Hodgkin's lymphoma (HL). However, there is limited experience of its efficacy and feasibility in older patients. The characteristics and outcomes of 121 patients aged ≥50 years (42 of them are ≥60 years old) with R/R HL who underwent AHCT were reviewed. After a median follow-up of 3.1 years, overall survival (OS) and progression-free survival (PFS) at 5 years were 64 and 55 %, respectively, with no differences between 50-59-year-old and ≥60-year-old patients. Hematological and extra-hematological toxicities after AHCT were comparable between the two groups of age. In univariate analysis, poorer OS and PFS were associated with disease status other than complete remission, hematopoietic cell transplantation comorbidity index (HCT-CI) scores >1, and Charlson Comorbidity Index (CCI) scores >1. HCT-CI scores >1 were also associated with a higher risk of grade 3-4 extrahematologic toxicity. In multivariate analysis, HCT-CI and CCI remained significantly associated with OS and PFS after adjustment for disease status. Our data show that AHCT can be performed in selected patients with R/R HL ≥50 years with acceptable outcome and toxicity. Comorbidities appear to impact AHCT outcome more than age.

Odelia A, Erel J, Chava P, et al.
Continuing dilemmas in the management of lymphoma during pregnancy: review of a 10-point case-based questionnaire.
Int J Clin Oncol. 2017; 22(1):190-199 [PubMed] Related Publications
INTRODUCTION: Due to the rarity of lymphoma during pregnancy, management guidelines are based upon evidence from retrospective studies and case reports. Here, we review the major dilemmas in the field and examine the approach of hemato-oncologists in Israel to the management of lymphoma in pregnancy.
METHODOLOGY: We performed a literature search on the PubMed database using keywords for all papers on the subject from 1990-2014. The papers were reviewed by an expert panel who devised a questionnaire covering the main dilemmas. Sixty questionnaires were sent out.
RESULTS: Non-contrast magnetic resonance imaging was the staging modality of choice. Chemoimmunotherapy was considered relatively safe beyond the first trimester except methotrexate (completed postpartum). Steroids or vinblastine were suggested by most as a reasonable 'bridging therapy' until the second trimester in Hodgkin lymphoma. The dosage of chemoimmunotherapy employed during pregnancy remained debatable; the majority recommended dosage according to actual pregnancy weight. Optimal timing for delivery was considered by most to be >35 weeks. Regarding approach to next pregnancy for patients in complete remission from diffuse large B-cell lymphoma, 69 % advised waiting 2 years but the majority advised 6-12 months for follicular lymphoma.
DISCUSSION: Despite consensus regarding the safety of chemotherapy post first trimester, optimal dosage, central nervous system therapy, timing of delivery and approach to future pregnancies remain controversial, indicating a need for further collaborative research in this field.

Hussain A, Tandon A, Prayaga AK, et al.
Cytomorphology and Histology Correlation of Rosai-Dorfman Disease: A 15-Year Study from a Tertiary Referral Centre in South India.
Acta Cytol. 2017; 61(1):55-61 [PubMed] Related Publications
OBJECTIVES: Rosai-Dorfman disease (RDD) is an uncommon, benign histiocytic disorder of unknown etiology, typically presenting in young adulthood. We highlight the cytomorphology of RDD and correlate it with the histopathology.
STUDY DESIGN: All cases diagnosed as RDD on fine-needle aspiration cytology between January 2001 and June 2015 were included. Clinical details were obtained from medical records. The cytology smears were reviewed along with the histopathology and immunohistochemistry, wherever available.
RESULTS: The study included 10 cases ranging in age from 11 to 68 years (median 29). There was a male predominance with a male:female ratio of 1.5:1. The patients commonly presented with bilateral cervical lymphadenopathy. Extranodal involvement was seen in 2 cases in the nose and mandible, respectively. Of these 10 cases, 8 were later biopsied. The cytological features included numerous crescentic histiocytes, emperipolesis, reactive lymphocytes and plasma cells. A histological diagnosis of RDD was made in 7 out of 8 cases, and 1 was diagnosed as Hodgkin lymphoma.
CONCLUSION: FNA represents an efficient, minimally invasive, cost-effective and reliable technique for the diagnosis of RDD and may obviate the need for further biopsy. However, the disease has close differential diagnoses, including Langerhans cell histiocytosis, granulomatous lesions, and Hodgkin lymphoma. Hence, it must be remembered that there can be pitfalls when the diagnosis is made by cytology alone.

Tănase A, Tomuleasa C, Mărculescu A, et al.
First Successful Haploidentical Stem Cell Transplantation in Romania.
Rom J Intern Med. 2016; 54(3):194-200 [PubMed] Related Publications
Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin's lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a prèmiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe.

Sultan S, Irfan SM, Parveen S, Ali S
Clinico-Hematological Findings for Classical Hodgkin's Lymphoma: an Institutional Experience.
Asian Pac J Cancer Prev. 2016; 17(8):4009-11 [PubMed] Related Publications
BACKGROUND: Classical Hodgkin's lymphoma (cHL) is a B-cell lymphoid neoplasm characterized by a distinctive biological behavior with potentially curable disease characteristics. It is an uncommon hematological malignancy which primarily affects younger individuals. The rationale of this study was to determine its clinico-hematological profile along with stage strati cation in Pakistani patients.
MATERIALS AND METHODS: In this descriptive study, adult patients with Hodgkin's lymphoma were enrolled from January 2010 to December 2014.
RESULTS: Sixty two histopathologically con rmed cases of cHL were identified. There were 42 males and 20 females, with a male to female ratio of 2:1. The mean age was 29.7±13.8 years with the median age of 30. B symptoms were present in 72.5% of patients. Histopathologically, the mixed cellularity type constituted 62.9% of cases, followed by nodular sclerosis in 25.8%, lymphocyte predominant in 9.6% and lymphocyte depleted in 1.6%. Stages I and II were present in 43.5% of patients at disease presentation, with 56.4% in stages III and IV.
CONCLUSIONS: Our analysis shows that clinico-pathological features of Hodgkin's lymphoma in Pakistan are comparable to published data. Mixed cellularity is the commonest histological variant and advanced stage at presentation are common findings in our patients.

Bur H, Haapasaari KM, Turpeenniemi-Hujanen T, et al.
Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma.
Anticancer Res. 2016; 36(9):4677-83 [PubMed] Related Publications
BACKGROUND: Epigenetic regulators, including Jumonji domain 2 (JMJD2/KDM4) proteins are involved in post-translational modification of histone demethylation and have a major role in carcinogenesis of many solid tumors.
MATERIALS AND METHODS: We assessed immunohistochemically the expression of lysine (K)-specific demethylase 4 (KDM4)A, KDM4B and KDM4D in tumors from 91 patients of adriamycin, bleomycin, vinblastine, darcabazine (ABVD)-treated classical Hodgkin lymphoma.
RESULTS: Strong cytoplasmic KDM4B expression in the reactive cellular infiltrate and also in Reed-Sternberg (RS) cells predicted poor relapse-free survival (RFS) (p=0.020 and p=0.022, respectively) in patients with limited-stage disease. Strong KDM4B expression in RS cells was also related to B-symptoms (p=0.007) and advanced stage (p=0.024). Strong KDM4D expression in the cytoplasm of RS cells was also associated with poor RFS in limited-stage patients RFS (p=0.043) and, most significantly, in patients receiving involved-field radiotherapy (p=0.007).
CONCLUSION: KDM4B and KDM4D expression may associate with an aggressive subtype of classical Hodgkin lymphoma and be linked with radioresistance.

Song HN, Kim SJ, Ko YH, Kim WS
Mediastinal Gray Zone Lymphoma with Features Intermediate between Classical Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma.
Acta Haematol. 2016; 136(3):186-90 [PubMed] Related Publications
BACKGROUND: Mediastinal gray zone lymphoma (MGZL) shares clinical characteristics with primary mediastinal B-cell lymphoma (PMBCL) and nodular sclerosing Hodgkin lymphoma (NSHL). However, MGZL is extremely rare, and an appropriate treatment for it has not yet been established.
METHODS: We retrospectively analyzed 8 patients who were treated with systemic chemotherapy for MGZL between 2007 and 2014.
RESULTS: The patients with MGZL were predominantly young and male (median age 26 years), and 62.5% of patients had bulky disease. The overall response rate (ORR) and complete remission (CR) rate were both 75% (6/8) for all treated patients The median overall survival (OS) and progression-free survival (PFS) was 40.7 and 3.9 months, respectively. Most responders (4/6, 66.7%) were treated with R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) as the frontline therapy. The CR rate of patients who received R-CHOP and those who did not was 100% (4/4) and 50% (2/4), respectively. Particularly striking was the finding that the median PFS of patients who received R-CHOP frontline chemotherapy was 11.4 months, which was superior to the median PFS of patients who did not receive R-CHOP.
CONCLUSIONS: Of the 8 patients with MGZL who were treated with systemic chemotherapy, superior treatment responses were observed in patients who received R-CHOP as the frontline therapy.

Afaq A, Fraioli F, Sidhu H, et al.
Comparison of PET/MRI With PET/CT in the Evaluation of Disease Status in Lymphoma.
Clin Nucl Med. 2017; 42(1):e1-e7 [PubMed] Related Publications
PURPOSE: The primary aim was to compare the diagnostic performance of PET/MRI (performed with basic anatomical MRI sequences) in detecting sites of disease in adult patients with lymphoma compared with the current standard of care, PET/CT. Secondary aims were to assess the additional value of diffusion-weighted imaging to PET/MRI in disease detection and to evaluate the relationship between the standardized uptake value on PET/MR and the apparent diffusion coefficient on diffusion-weighted imaging.
METHODS: Sixty-eight studies in 66 consecutive patients with histologically proven Hodgkin or non-Hodgkin lymphoma were prospectively evaluated. Each patient had whole body PET/CT, followed by whole body PET/MR. Two experienced readers independently evaluated the PET/MRI studies, and two other experienced readers independently evaluated PET/CT. Site of lymphoma involvement and SUVmax at all nodal sites more avid than background liver were recorded. Readers provided stage (in baseline cases) and disease status (remission vs active disease). The apparent diffusion coefficient mean value corresponding to the most avid PET site of disease was recorded.
RESULTS: Ninety-five nodal and 8 extranodal sites were identified on both PET/CT and PET/MRI. In addition, 3 nodal and 1 extranodal sites were identified on PET/MRI. For positive lesion detection, reader agreement in PET/MR was perfect between the 2 readers and almost perfect between PET/CT and PET/MR (k > 0.978). Intermodality agreement between PET/CT and PET/MRI was also near perfect to perfect for staging/disease status k = (0.979-1.000). SUVmax from PET/CT and PET/MRI correlated significantly (Spearman rho correlation coefficient, 0.842; P < 0.001). Diffusion-weighted imaging did not alter lesion detection or staging in any case. A negative correlation was demonstrated between ADC mean and SUVmax (Spearman rho correlation coefficient r, -0.642; P < 0.001).
CONCLUSIONS: PET/MRI is a reliable alternative to PET/CT in the evaluation of patients with lymphoma. Diffusion-weighted imaging did not alter diagnostic accuracy. With comparable accuracy in detection of disease sites and added benefit of radiation dose reduction, PET/MRI has a potential to become part of routine lymphoma imaging.

Stacchini A, Demurtas A, Aliberti S, et al.
Single-Tube Flow Cytometry Assay for the Detection of Mature Lymphoid Neoplasms in Paucicellular Samples.
Acta Cytol. 2016; 60(4):385-394 [PubMed] Related Publications
OBJECTIVES: Flow cytometry (FC) has become a useful support for cytomorphologic evaluation (CM) of fine-needle aspirates (FNA) and serous cavity effusions (SCE) in cases of suspected non-Hodgkin lymphoma (NHL). FC results may be hampered by the scarce viability and low cellularity of the specimens.
STUDY DESIGN: We developed a single-tube FC assay (STA) that included 10 antibodies cocktailed in 8-color labeling, a cell viability dye, and a logical gating strategy to detect NHL in hypocellular samples. The results were correlated with CM and confirmed by histologic or molecular data when available.
RESULTS: Using the STA, we detected B-type NHL in 31 out of 103 hypocellular samples (81 FNA and 22 SCE). Of these, 8 were not confirmed by CM and 2 were considered to be only suspicious. The FC-negative samples had a final diagnosis of benign/reactive process (42/72), carcinoma (27/72), or Hodgkin lymphoma (3/72).
CONCLUSIONS: The STA approach allowed obtainment of maximum immunophenotyping data in specimens containing a low number of cells and a large amount of debris. The information obtained by STA can help cytomorphologists not only to recognize but also to exclude malignant lymphomas.

Shao F, Wu J, Huang Z, et al.
Serendipitous Detection of Hodgkin Lymphoma by 18F-NaF PET/CT.
Clin Nucl Med. 2016; 41(10):815-8 [PubMed] Related Publications
A 17-year-old girl underwent F-NaF PET/CT to evaluate bone pain after an accident. The images did not identify any osseous lesion. However, there was a focally increased activity in the left upper chest, which corresponded to a partially calcified soft tissue mass in the mediastinum, suggestive of malignancy. The result led to subsequent F-FDG PET/CT imaging, which demonstrated intense activity in the mediastinal mass and in multiple cervical, supraclavicular, and mediastinal lymph nodes. Hodgkin lymphoma was diagnosed histopathologically following the biopsy.

Alicandro G, Rota M, Boffetta P, La Vecchia C
Occupational exposure to polycyclic aromatic hydrocarbons and lymphatic and hematopoietic neoplasms: a systematic review and meta-analysis of cohort studies.
Arch Toxicol. 2016; 90(11):2643-2656 [PubMed] Related Publications
Data on the risk of lymphatic and hematopoietic neoplasms among workers whose jobs entail high exposure to polycyclic aromatic hydrocarbons (PAH) are sparse, and mainly based on small-size studies. We carried out a systematic review of occupational cohort studies that reported results on incidence or mortality from Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), leukemia or multiple myeloma (MM) among workers exposed to PAH. We computed meta-analytic estimates using a random effect model. Meta-relative risk (meta-RR) was computed separately by each type of neoplasm, job or industry. We identified 41 studies (12 in iron and steel foundries, 11 in aluminum plant, 6 in cokeries, 6 in carbon electrode manufacturing, 2 on asphalt workers, 2 on creosote-exposed workers, 1 on tar distillery workers and 1 evaluating both tar distillery workers and roofers). No significant excess risk of any lymphatic and hematopoietic neoplasms was found among workers employed in jobs or industries entailing high PAH exposure. Among 18 meta-analytic estimates by job or industry and type of neoplasm, 16 were close to unit, i.e., between 0.72 and 1.27, whereas the meta-RR was 1.38 [95 % confidence interval (CI) 0.95-2.01] for HL in foundry workers and 2.01 (95 % CI 0.96-4.22) for NHL in workers exposed to creosote. There was no association between occupation entailing high PAH exposure and risk of MM or leukemia.

Adams HJ, Kwee TC
Controversies on the prognostic value of interim FDG-PET in advanced-stage Hodgkin lymphoma.
Eur J Haematol. 2016; 97(6):491-498 [PubMed] Related Publications
Hodgkin lymphoma, even in advanced-stage, is a highly curable malignancy, but treatment is associated with short-term toxicity and long-term side effects. Early predictive markers are required to identify those patients who do not require the full-length standard therapy (and thus qualify for therapy de-escalation) and those patients who will not be cured by standard therapy (and thus qualify for therapy escalation). Multiple trials have assessed the value of (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) after a few cycles of chemotherapy (also known as 'interim FDG-PET') in predicting outcome in advanced-stage Hodgkin lymphoma. Furthermore, multiple interim FDG-PET-adapted trials, in which patients with positive interim FDG-PET scans are assigned to escalated therapies, and patients with negative interim FDG-PET scans are assigned to de-escalated therapies, have recently been published or are currently ongoing, with generally heterogeneous results. The present article reports the currently available evidence (and controversies) on the prognostic value of interim FDG-PET in advanced-stage Hodgkin lymphoma in patients with positive and negative interim FDG-PET findings following continuation of standard chemotherapy or escalated/de-escalated therapy.

Lancelot S, Giammarile F, Tescaru A
Paraneoplastic syndrome demonstrated on (99m)Tc-HMDP bone scan.
Eur J Nucl Med Mol Imaging. 2016; 43(12):2271-2272 [PubMed] Related Publications
A 23-year-old man, with no relevant medical history, presented with inflammatory peripheral and axial polyarthritis, wrist pain, and persistent low-grade fever for the past 4 months. A bone scintigraphy showed intense periosteal early and delayed uptake in long bones, with normal uptake in the spine, pelvis, and rib cage, and no clear focus of hypermetabolism. CT scan revealed a mediastinal mass. A biopsy of the mass demonstrated Hodgkin lymphoma with bulky disease. This paraneoplastic syndrome as the first sign of intrathoracic Hodgkin's disease is rare.

Ng AK, van Leeuwen FE
Hodgkin lymphoma: Late effects of treatment and guidelines for surveillance.
Semin Hematol. 2016; 53(3):209-15 [PubMed] Related Publications
Long-term survivors of Hodgkin lymphoma (HL) are at risk for a range of late effects, with second malignant neoplasm and cardiovascular diseases being the leading causes of death in these patients. The excess risks remain significantly elevated decades after treatment, and are clearly associated with extent of treatment exposures. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies, muscle atrophy, and persistent fatigue. Systemic documentation of late effects and recognition of treatment- and patient-related risk factors are important, as they inform optimal surveillance and risk-reduction strategies, as well as guide therapeutic modifications in newly diagnosed patients to minimize treatment-related complications. As HL therapy evolves over time, with adoption of novel agents and contemporary treatment techniques, late effect risks and follow-up recommendations need to be continuously updated.

Bachanova V, Connors JM
Hodgkin lymphoma in the elderly, pregnant, and HIV-infected.
Semin Hematol. 2016; 53(3):203-8 [PubMed] Related Publications
Hodgkin lymphoma (HL) presenting in patients with co-incidental advanced age, pregnancy, or human immunodeficiency virus (HIV) infection is uniquely challenging to manage. In this article we integrate recent evidence and clinical expertise to present recommendations for diagnosis and therapeutic management. Older patients with HL need to be carefully evaluated for comorbidies after which judicious choice of chemotherapy should minimize functional compromise. A pregnant patient with concurrent HL should be staged with minimal use of imaging requiring ionizing radiation and treated in an individualized manner optimally combining the strategies of treatment deferral when appropriate, use of single-agent vinblastine for symptomatic disease and reservation of multi-agent chemotherapy for the small minority of patients with aggressive clinical presentation. Treatment of HL coincident with HIV infection requires a combination of highly active anti-retroviral agents (HAART), standard multi-agent chemotherapy with meticulous attention to drug-drug interactions, and vigorous supportive care to ensure the best chance of cure.

Savage KJ, Mottok A, Fanale M
Nodular lymphocyte-predominant Hodgkin lymphoma.
Semin Hematol. 2016; 53(3):190-202 [PubMed] Related Publications
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL.

Younes A, Ansell SM
Novel agents in the treatment of Hodgkin lymphoma: Biological basis and clinical results.
Semin Hematol. 2016; 53(3):186-9 [PubMed] Related Publications
Hodgkin Lymphoma (HL) is a lymphoproliferative disorder of B cells that commonly has a favorable prognosis when treated with either combination chemotherapy and radiation therapy, or chemotherapy alone. However, the prognosis for patients who relapse, or have evidence for refractory disease, is poor and new treatments are needed for patients with progressive disease. HL has a unique tumor microenvironment consisting of a predominance of inflammatory cells and a minority of malignant Hodgkin and Reed-Sternberg (HRS) cells. This unique biology provides an opportunity for novel therapy approaches that either specifically target the malignant HRS cell or target the inflammatory tumor microenvironment. New therapies including antibody drug conjugates targeting CD30, small molecule inhibitors that inhibit critical cell signaling pathways, monoclonal antibodies that block immune checkpoints, or agents that modulate the immune microenvironment have all recently been tested in HL with significant clinical activity. Multiple clinical trials are currently ongoing testing these agents in the relapsed and refractory setting but also in earlier phases of therapy often in combination with more standard treatment.

von Tresckow B, Moskowitz CH
Treatment of relapsed and refractory Hodgkin Lymphoma.
Semin Hematol. 2016; 53(3):180-5 [PubMed] Related Publications
Despite the high first-line cure rates in patients with Hodgkin Lymphoma (HL) still 10%-20% of patients suffer from relapsed or refractory disease. High-dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) is standard of care for suitable patients with relapsed or refractory HL and allows for cure in approximately 50%. Due to the poor prognosis of high-risk patients even with HDCT and ASCT, consolidation strategies have been evaluated to improve the cure rates. For patients with recurrence after HDCT and ASCT, treatment is palliative in most cases. The anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) has been shown to induce high response rates in these patients; however, durable responses were reported in a small percentage of patients only. For carefully selected patients with multiple relapses, dose-reduced allogeneic transplant (RICallo) is a potentially curative option. The role of RICallo will have to be re-evaluated in the era of anti-programmed death-1 (PD1) antibodies.

Vassilakopoulos TP, Johnson PW
Treatment of advanced-stage Hodgkin lymphoma.
Semin Hematol. 2016; 53(3):171-9 [PubMed] Related Publications
There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%-20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody-drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this.

Engert A, Raemaekers J
Treatment of early-stage Hodgkin lymphoma.
Semin Hematol. 2016; 53(3):165-70 [PubMed] Related Publications
Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed.

Bröckelmann PJ, Angelopoulou MK, Vassilakopoulos TP
Prognostic factors in Hodgkin lymphoma.
Semin Hematol. 2016; 53(3):155-64 [PubMed] Related Publications
During the last decades, the prognosis of Hodgkin lymphoma (HL) has been improved significantly with the introduction of effective chemotherapy and the implementation of risk-adapted treatment approaches. Identification of reliable risk factors is crucial to guide treatment over the course of disease. Both clinical and biological factors have been implicated in the prognosis of HL and are often used in prognostic scores to discriminate risk groups. To prevent under- or overtreatment, patients are usually assigned to one of the three widely established risk groups for first-line treatment, based solely on clinical risk factors. To further individualize therapeutic approaches, functional imaging with positron emission tomography (PET) is becoming more widely implemented and precisely investigated within clinical trials. Biological prognostic factors have been widely evaluated but are still not a part of standard prognostication. This review will discuss the currently established factors and risk models at first diagnosis and in the setting of relapsed/refractory disease and also focus on biological factors and PET, summarizing current standards and future perspectives.

Gallamini A, Hutchings M, Ramadan S
Clinical presentation and staging of Hodgkin lymphoma.
Semin Hematol. 2016; 53(3):148-54 [PubMed] Related Publications
In the present chapter the authors present a brief overview of the diagnostic methods proposed over time for Hodgkin lymphoma (HL) spread detection, moving from surgical procedures, through standard radiological and functional imaging techniques to the present state of the art for HL staging. The main body of the review will be dedicated to the recently published guidelines for lymphoma staging (including HL) agreed by the experts during the 12th International Congress for Malignant Lymphoma in Lugano. The recommendations of the panel on how to integrate flurodeoxyglucose positron emission tomography (FDG-PET) scan in the armamentarium of staging procedures will be presented and commented, with a special emphasis on the utility of special procedures, such as bone marrow trephine biopsy, which is deemed no longer needed in the PET era. While the HL diagnosis is straightforward in most cases, sometimes HL is a subtle disease, difficult to diagnose for the paucity of symptoms, the absence of physical findings, or for concomitant immunologic disorders: a compete overview of the common and rare patterns of HL clinical presentation will be also offered. The future perspective of PET scan use will be based on a operator-independent, quantitative readings of the scan thanks to a plethora of sophisticated dedicated software, which are now available, able to quantify every voxel captured by the tumor to display the metabolically active tumor volume. Moreover, new tracers are now available able to track the new pathways of cellular metabolism beside glycolysis such as amino acids or purine-analogues or specific oncoproteins; the preliminary, promising results will be reported. Preliminary results from other imaging techniques, such as diffusion-weighted magnetic resonance (DW-MRI) will be also reported.

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