The prognostic significance of cellular subtypes in nodular sclerosing Hodgkin's disease: An analysis of 271 non-laparotomised cases (BNLI report no. 22)

doi:10.1016/S0009-9260(83)80148-2

Clinical Radiology

Volume 34, Issue 5, January–November 1983, Pages 497-501

https://doi.org/10.1016/S0009-9260(83)80148-2 Get rights and content

A histological review of 271 cases of nodular sclerosing Hodgkin's disease, patients presenting with clinical Stage I, II and III disease but not subjected to a staging laparotomy, has been undertaken. Cases were categorised according to the cytological appearances of the cellular nodules and the degree of sclerosis was examined. Cytological subtypes with extensive and easily recognised areas of lymphocyte depletion or numerous pleomorphic Hodgkin's cells were associated with a decreased survival and clinical stage did not appear to be a good indicator of prognosis in these patients. Pronounced nodal sclerosis was associated with a higher relative frequency of mediastinal disease and the lymphocyte-depleted cytological subtypes.

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Very few neoplastic diagnostic cells (Reed Sternberg cells) [13,14] are present within inflammatory tissues containing a variable number of small lymphocytes, eosinophils, neutrophils, macrophages, plasma cells, fibroblasts, and collagen fibers. This case points out how challenging the diagnosis of Hodgkin’s disease can be, and the impact that a diagnostic delay can have in the prognosis [15,16] of a life-threatening condition. The acute and atypical symptoms (pain, dyspnoea, sternal oedema) misled us, letting to the suspicious of a benign disease.
The diagnostic approach to patients with mediastinal pathology is not always simple and an improper diagnostic work-up can lead to significant diagnosis delay.
: We report on the case of a young woman who was admitted to the Emergency Department complaining of thoracic pain, dyspnoea, fever and productive cough. The physical examination showed a painful swelling over the sternum’s upper left margin, which had become evident 4 months earlier. A Computer Tomography showed the presence of a retrosternal oval lesion (5.5 x 4 cm) infiltrating the thoracic wall and showed the presence of discretely enlarged mediastinal lymph nodes in several mediastinal stations.
The Multidisciplinary Team decided to perform an ultrasound-guided biopsy of the retrosternal mass that showed an inflammatory pattern, whereas microbiology tests proved negative. The lack of improvement with medical therapy (non steroideal anti-inflammatories and antibiotics) and the clinical suspicion of malignancy led us to perform a surgical biopsy of the mass that finally proved to be diagnostic for Hodgkin’s lymphoma.
Mediastinal masses with an aggressive behavior, should always be considered to be potentially malignant. Surgical biopsy, sometimes, can be the only way to correctly diagnose the pathological process, especially in the case of Hodgkin’s lymphoma in which few diagnostic cells (Reed-Sternberg cells) are generally embedded in an abundant inflammatory background tissue.
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Does bulky disease at diagnosis influence outcome in childhood Hodgkin's disease and require higher radiation doses? Results from the German-Austrian Pediatric Multicenter Trial DAL-HD-90
2003, International Journal of Radiation Oncology Biology Physics
The identification of risk factors is required for risk-adapted treatment strategies in the treatment of Hodgkin’s disease. To assess the influence of bulky disease at diagnosis as compared with other risk factors on event-free survival (EFS) in pediatric Hodgkin’s disease such as stage, B-symptoms, number of involved lymph node regions, histology, and remission status after chemotherapy, we analyzed the outcome of 552 patients treated with a risk-adapted treatment strategy consisting of OPPA(OEPA)/COPP (vincristine, procarbazine, etoposide, prednisone, adriamycin, cyclophosphamide) and involved-field radiotherapy.
Between 1990 and 1995, 578 patients with primary Hodgkin’s disease (HD) were enrolled in the German/Austrian Pediatric Hodgkin’s Disease Study Group (DAL) Multicenter Study (HD-90). Patients were stratified into three treatment groups (TGs) for early, intermediate, and advanced stage. All patients received induction chemotherapy (CT) with two cycles of OEPA for boys and two cycles of OPPA for girls. Patients in TG2 and TG3 received another two or four cycles, respectively, of COPP. Chemotherapy was followed by involved-field radiotherapy. The radiation field, which was prescribed by the study center, was treated with a dose of 25 Gy/25 Gy/20 Gy (TG1/TG2/TG3), and in case of insufficient remission with a local boost of 5 Gy to 10 Gy. The following prognostic factors were analyzed with regard to their impact on EFS: bulky disease, mediastinal tumor, number of involved lymph node regions, histology, treatment group, B-symptoms, sex, age, and remission status after chemotherapy.
Significant univariate predictive factors for EFS were: nodular sclerosis type 2 (NS2) histology (relative risk [RR] 3.43; p = 0.0002), presence of B-symptoms (RR 2.70; p = 0.0014), number of involved regions (1.55; p = 0.019), and treatment groups (RR 1.33; p = 0.017). There was a higher risk (RR 1.92; p = 0.040) for patients with bulky compared with nonbulky disease (5-year EFS 89.6%/94.6%). In the multiple regression model, only NS2 and B-symptoms remained strong predictive factors. The remission status after chemotherapy did not correlate with EFS (p = 0.66).
Treatment strategies in Hodgkin’s disease have an impact on different risk factors. In the risk-adapted treatment strategy of the HD-90 study, tumor burden indicated as bulky disease or as number of involved lymph nodes loses its importance, whereas NS2 histology and B-symptoms have a major impact on treatment outcome. Bulky disease at diagnosis might require higher radiation doses only in case of insufficient remission.
Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease
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Citation Excerpt :
The CD30+, CD45−, CD15+, and EMA− diagnostic profile was required for the diagnosis of common HD. The revised European-American classification of lymphoid neoplasms (REAL)29 was used to classify the histologic subtypes of HD; the nodular sclerosis (NS) subtype was classified as NS I or NS II according to the British National Lymphoma Investigation.30 Immunostaining with c-MET rabbit polyclonal antibody (pAb) and with antihuman HGF goat antiserum was performed on frozen sections and on formalin-fixed paraffin-embedded tissues.
The receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met. Recently, c-MET was detected in Reed-Sternberg (RS) cells from Epstein-Barr virus–positive (EBV⁺) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph node biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease. In all 45 lymph node and 12 bone marrow samples examined, RS cells expressed c-MET but not HGF⁺. These results were independent of the EBV infection. Interestingly, several HGF⁺ dendritic-reticulum cells were found scattered around c-MET⁺ RS cells. The mean ± SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 ± 91 (95% confidence interval [CI], 1221-1585) and 1497 ± 242 pg/mL (95% CI, 977-2017), respectively. HGF values were significantly higher than those of healthy individuals (665 ± 28 pg/mL; 95% CI, 600-721; and P < .001 for both groups of patients) and of HD patients in remission (616 ± 49 pg/mL; 95% CI, 517-714; andP < .001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (P = .014). In conclusion, this study indicates that HGF and c-MET constitute an additional signaling pathway between RS cells and the reactive cellular background, thereby affecting adhesion, proliferation, and survival of RS cells. Furthermore, the serum concentration of HGF in HD patients may be a useful tool in monitoring the status of disease.

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The prognostic significance of cellular subtypes in nodular sclerosing Hodgkin's disease: An analysis of 271 non-laparotomised cases (BNLI report no. 22)

Clinical Radiology

Clinical Radiology

Prognostic significance of histologic subdivision of Hodgkin's disease nodular sclerosis

Acta Radiologica Oncology

A clinicopathological study of nodular sclerosing Hodgkin's disease

Journal of Clinical Pathology

Curability of advanced Hodgkin's disease with chemotherapy

Annals of Internal Medicine

New assessment of the prognostic significance of histopathology in Hodgkin's disease for laparotomy negative Stage I and II patients

Cancer

Hodgkin's Disease