Nodular Sclerosing Hodgkin's Disease Research Articles

Recurrent “syncytial variant” of Hodgkin's disease: An immunohistologic diagosis

A case of recurrent Hodgkin's disease of the "sarcomatoid" or "syncytial variant" type was seen that occurred as an extension from the mediastinum to a previously uninvolved extranodal site (breast) and pericardium after treatment of classical nodular sclerosing Hodgkin's disease based in the lymph nodes. This histologic variant was composed of sheets of large, undifferentiated neoplastic cells with few, if any, diagnostic features of nodular sclerosing Hodgkin's disease. For this reason, the differential diagnosis of this variant was difficult and included non-Hodgkin's lymphoma (peripheral T-cell lymphoma), Ki-1-positive lymphoma, medullary carcinoma, metastatic carcinoma, melanoma, and granulocytic sarcoma. Immunologic analysis by immunoperoxidase technique showed a phenotype consistent with "syncytial variant" Hodgkin's disease: Leu-M1+, Ki-1+, IL-2+, HLA-DR+, T11-, pan B-, K-, lambda-, cytokeratin-, S-100-, muramidase-.

Reed-Sternberg and Hodgkin cells in lymphocyte-predominant Hodgkin's disease of nodular subtype contain J chain.

To throw light on the question of whether B-cell-derived forms of Hodgkin's disease exist, more than 100 cases of Hodgkin's disease (including all four major histologic categories) were investigated for the presence of J chain and were also immunostained for epithelial membrane antigen and the granulocyte-associated antigen X hapten. Reed-Sternberg and Hodgkin cells (RS & H) expressed J chain in 22 cases, 8 of which also expressed epithelial membrane antigen (EMA). X hapten was found in 62 cases, but all of these were J chain negative. J chain-positive RS & H cells were restricted to cases of lymphocyte-predominant disease, while X hapten-positive tumor cells were found frequently in nodular sclerosis, mixed cellularity, and lymphocyte-depletion Hodgkin's disease, but only occasionally in cases of lymphocyte-predominant disease. These findings indicate that nodular lymphocyte-predominant Hodgkin's disease differs from the other subtypes of Hodgkin's disease and that the neoplastic cells are of B-lymphoid origin.

Intrathoracic Hodgkin's disease a case presentation with multiple pulmonary nodules in the absence of mediastinal or Hilar node disease

Patients with Hodgkin's disease (HD) most commonly present with peripheral lymph node enlargement. The finding of pulmonary parenchymal involvement is usually associated with hilar and/or mediastinal adenopathy; such instances are felt to represent spread to the lung by contiguity. Noncontiguous spread to peripheral lung parenchyma in the absence of hilar or mediastinal node involvement has rarely been reported. This is the first documented case report in a 32-year-old woman with nodular sclerosing HD. The unusual clinical presentation in this patient was associated with the histologic detection of vascular invasion in the lymph node and open-lung biopsy specimens.

B- and T-lymphocytes in Hodgkin's disease. An immunohistochemical study utilizing heterologous and monoclonal antibodies.

Immunohistologic techniques utilizing monoclonal antibodies have made possible the identification of leukocytes by their phenotypic characteristics rather than by morphologic features alone. A panel of antibodies for T-lymphocyte, B-lymphocyte, and monocyte/histiocyte markers has been applied to frozen sections of nodular sclerosing and mixed cellularity Hodgkin's disease to identify more precisely the various cell types present in tissues involved in Hodgkin's disease. The majority of lymphocytes expressed detectable T-cell phenotypic markers, with a predominance of the "helper" phenotype (Leu 3/OKT4) in most cases. Lymphocytes reacting with anti-B-cell antibodies were also demonstrated; their distribution is described here and has not previously been reported. The anti-B- and anti-T-cell antibodies used in this study failed to give positive reactivity with Reed-Sternberg cells. However, one of the anti-monocyte antibodies (Leu-M1) reacted with diagnostic Reed-Sternberg cells in some cases. The patterns of staining observed varied widely within the two histologic types of Hodgkin's disease, leading to a conclusion that this disease may be more heterogeneous than is currently suspected.

HODGKIN-CELL LEUKAEMIA OF B-CELL ORIGIN

A case of lymphocyte-depleted nodular sclerosing Hodgkin's disease with a terminal leukaemic phase is described. Circulating Hodgkin cells were shown to be of B-cell origin by immunological phenotyping and the demonstration of clonal immunoglobulin gene rearrangement.

Isolation of activated ras transforming genes from two patients with Hodgkin's disease

Despite impressive advances in the clinical management of Hodgkin's disease, litle is known about its cellular origin or the mechanism(s) of “Hodgkinogenesis.” Recent findings that certain human cellular oncogenes can cause malignant transformation suggest that aberrant activation of these genes may play a role in carcinogenesis. To determine if such genes are operative in Hodgkin's cells, we isolated DNA from splenic nodules of three patients with nodular sclerosis Hodgkin's disease and tested its ability to transform mouse NIH 3T3 cells, the standard assay for oncogene-mediated malignant transformation. Transformed cells containing human DNA were obtained from two patients. DNA from these primary transformants yielded secondary transformants of NIH 3T3 fibroblasts; one also transformed normal mouse bone marrow macrophages, a cell type probably related to the Hodgkin's cell. When analyzed by Southern blot methods for homology with closed oncogene probes, the transforming genes from both patients had homology with N- ras. The homology and size of the restriction fragments were similar to those of transforming genes isolated from patients with acute nonlymphocytic leukemias. The presence of the same activated oncogene in tumor tissue from two different patients suggests that it may play an important role in Hodgkinogenesis.

Nodular Sclerosing Hodgkin's Disease of the Orbit

Hodgkin's disease is a rare occurrence in the orbit and, when present, has been seen in patients as part of the known systemic diasthesis usually in the terminal phase. A case of nodular sclerosing Hodgkin's with a long-standing lesion of the orbit leading to bony excavation in the lacrimal fossa is reported

Potentiation of Fibroblast Growth by Nodular Sclerosing Hodgkin's Disease Cell Cultures

Abstract Cell cultures were established from 8 lymph nodes replaced by nodular sclerosing Hodgkin's disease. Serum-containing and serum-free conditioned media from these cultures potentiated fibroblast growth and were found to be consistently more potent than fibroblast growth factor, 100 ng/ml, every other day. Both a proliferative response and transformation-like growth were observed using BALB/c 3T3 cells, human diploid fibroblasts, and human embryonic fibroblasts as target cells. The Hodgkin's disease growth factor(s) was not produced by fibroblasts or lymphocytes in the Hodgkin's cultures and was most potent when the Hodgkin's cultures had been enriched with Hodgkin's giant cells. Removal of normal macrophages decreased the proliferative activity but did not eliminate it or nonadherent growth of 3T3 cells in agar. Control cultures of 6 nonmalignant lymph nodes, a Lennert's lymphoma, a mixed cellularity Hodgkin's disease lymph node, and a malignant histiocytosis cell line suggested that among lymph node disorders, this feature may be relatively specific for nodular sclerosing Hodgkin's disease.

Nodular Sclerosing Hodgkinʼs Disease Presenting as Nephrotic Syndrome

A case of nephrotic syndrome due to minimal change renal disease was associated with minimally symptomatic nodular sclerosing Hodgkin's disease in a 15-year-old girl. Although minimal renal disease is the most frequently described biopsy finding in this paraneoplastic syndrome, the combination of nodular sclerosing Hodgkin's disease and minimal renal disease is uncommon. Four cases of this association have been reported in the literature. This case makes five.

Lymphoma of the breast.

Thirteen patients with lymphoma of the breast are presented. In addition, 163 previously reported cases of lymphoma of the breast are reviewed. Complete staging was performed on all patients. No patient had a diagnosis of lymphoma prior to breast biopsy. The histologic findings were diffuse histiocytic lymphoma (DHL) in eight patients, nodular lymphocytic poorly differentiated lymphoma (NLPD) in two patients, nodular mixed lymphoma (NM) in two patients and nodular sclerosing Hodgkin's disease (NSHD) in one patient. Five patients had Stage IV disease, two had Stage III disease, four had stage II disease and two Stage I disease. Nine patients each underwent an excisional biopsy and four patients each had a modified radical mastectomy as initial therapy. Two patients each underwent a staging laparotomy. In advanced disease, chemotherapy achieved complete remissions in approximately 50% of patients. Unfavorable histologic findings are most common in lymphoma of the breast and thorough staging is necessary to select the best form of therapy. The absolute survival rate (61%) and the disease free survival rate (46%) are similar to nodal lymphoma of corresponding histologic factors and stage.

Analysis of Grade 1 Hodgkin's disease (report no 6)

A review of the histology slides of 85 patients included in the BNLI clinical trials as lymphocyte predominant Hodgkin's disease has been undertaken. As a result of this review a number of conclusions have been drawn which affect the classification, staging, prognosis and management of Hodgkin's disease. A review of the histology slides of 85 patients included in the BNLI clinical trials as lymphocyte predominant Hodgkin's disease was undertaken because an unexpectedly high proportion (33%) had been found to be Stages III and IV and the overall survival at eight years (73%) did not differ significantly from that of nodular sclerosis or mixed cellularity Hodgkin's disease in the same trials (Fig. 1, Part 2). For the histological review the histological criteria as described by Lukes (1971) were rigidly adhered to. Cases were subdivided as follows: LP when lymphocytes predominated. L/H when there was a mixture of lymphocytes and histiocytes.

Histologic subclassification of nodular sclerosis Hodgkin's disease.

Nodular sclerosis (NS) Hodgkin's disease was pathologically subdivided by cellular composition and degree of fibrosis in a series of 49 children admitted to the Istituto Nazionale Tumori of Milan between 1967 and 1977. NS showed lymphocytic predominance (LP) in 26 cases, mixed cellularity (MC) in 16 cases, and lymphocytic depletion (LD) in 7 cases. "Early fibrosis" (EF) and "advanced fibrosis" (AF) subgroups in 28 and 21 cases, respectively, were observed. Of the cases with LP 76.9% (20/26) presented with stages I and II disease, compared with 37.5% (6/16) and 28.6% (2/7) of the MC nad LD subgroups, respectively. LP and EF subgroups coexisted in 12 of 28 (42.9%) patients at stages I and II. Predominance of lymphocytes, rarity of lacunar cells, and a mild degree of fibrosis were asociated with early stages of disease. This data confirms that subclassification of NS is feasible.

Hodgkin's disease in children. Pathologic study of 87 cases.

From 1963 to 1977 at the Istituto Nazionale Tumori at Milan, 112 patients below the age of 16 years with Hodgkin's disease (HD) were observed, representing 13.2% of all the cases of this disease seen during the stated time interval. Eighty-seven of these cases are the subject of the present study. Fifty-nine patients were males and 28 females (2.1:1 ratio). The age range varied from 2 years 10 months to 15 years 10 months (median 10 years). Forty-three (49.4%) children, of whom 35 were males and 8 females, were below the age of 10 years at the onset of their disease. The clinical staging resulted in 34 patients as stage I, 33 as stage II, 13 as stage III and 7 as stage IV. The histologic type was nodular sclerosis (NS) in 49 cases (56.3%), lymphocytic predominance (LP) in 15 cases (17.2%), mixed cellularity (MC) type in 9 cases (10.3%) and lymphocytic depletion (LD) in 8 cases (9.2%). In the remaining 6 cases the histologic classification was not applicable. LP type in 15/15 (100%) patients was associated with stages I and II, and NS in 38/49 (77%) patients was related to stage I and stage II. The latter was also the istologic type most often encountered in patients with stage II disease (23/33 or 70%). Eleven patients have died, and their survival varied from 6 to 47 months (median 30 months). The histologic type was LD in 4 cases, NS in 3 cases, MC in 1 case, and LP in 1 case. In the other 2 nonsurvivors, the histologic type was not identifiable. Of the 23 patients with more than a 5-year survival, 14 (60.8%) had NS HD. As in adults, LP and NS were associated with early stages of the disease and with long survival.

Comprehensive radiotherapy for advanced Hodgkin's disease refractory to chemotherapy.

Seven patients with advanced nodular sclerosing Hodgkin's disease who relapsed after initial intensive combination chemotherapy were selected for individualized pathologic restaging and comprehensive radiotherapy. One patient failed to respond completely to mantle-field irradiation and no further staging or radiotherapy was undertaken. Six other patients underwent staging laparotomy and received total nodal irradiation including prophylactic lung irradiation (5 cases) and hepatic irradiation (3 cases). Irradiation was well tolerated. Complete remission was achieved by 5 patients and 2 continue in remission 29+ and 32+ months after beginning of irradiation. Five of the 7 patients remain alive. This study indicates that comprehensive irradiation is a relatively well tolerated and effective treatment for carefully selected patients with advanced Hodgkin's disease who have relapsed after combination chemotherapy. For selected patients, pathologic restaging and comprehensive radiotherapy can be considered as an alternative to further chemotherapy.

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

Sixty-seven patients with nodular sclerosis (Hodgkin's disease stages I and II) have been subclassified according to the cellular composition and the amount of fibrosis. Predominance of mature lymphocytes and rarity of Reed Sternberg cells were associated with less extensive disease at presentation and more favourable outcome. A less definite correlation to the amount of fibrosis was found.

Contributions of Computed Tomography in the Staging and Management of Malignant Lymphoma

Pretreatment staging is considered essential in the management of patients with malignant lymphoma, particularly nodular sclerosing Hodgkin disease. The results of CT examination of 33 patients with malignant lymphoma are correlated with the results of lymphangiography, nuclide images of the liver and spleen, gallium citrate57 images of lymphoid tissue, and nuclide bone images. CT is least effective in the early clinical stages of malignant lymphoma because normal or minimally enlarged nodes are difficult to detect; CT is probably reliable enough to replace lymphangiography of gallium57 imaging in patients with advanced disease.

Comprehensive radiotherapy for advanced Hodgkin's disease refractory to chemotherapy

Seven patients with advanced nodular sclerosing Hodgkin's disease who relapsed after initial intensive combination chemotherapy were selected for individualized pathologic restaging and comprehensive radiotherapy. One patient failed to respond completely to mantle-field irradiation and no further staging or radiotherapy was undertaken. Six other patients underwent staging laparotomy and received total nodal irradiation including prophylactic lung irradiation (5 cases) and hepatic irradiation (3 cases). Irradiation was well tolerated. Complete remission was achieved by 5 patients and 2 continue in remission 29+ and 32+ months after beginning of irradiation. Five of the 7 patients remain alive. This study indicates that comprehensive irradiation is a relatively well tolerated and effective treatment for carefully selected patients with advanced Hodgkin's disease who have relapsed after combination chemotherapy. For selected patients, pathologic restaging and comprehensive radiotherapy can be considered as an alternative to further chemotherapy.

Undifferentiated Sarcoma

SARCOMAS of the chest wall appearing after postoperative radiation therapy for breast carcinoma have recently been reviewed by Travis et al.1Less well documented are instances of such tumors developing in persons receiving nodal and mediastinal irradiation for Hodgkin's disease. We report such an occurrence. Report of a Case A 42-year-old woman, in 1969, had a history of fever, pruritis, and enlarged cervical lymph nodes, which were diagnosed by node biopsy as having nodular sclerosing Hodgkin's disease. Chest roentgenograms demonstrated a widened mediastinum and a large mediastinal mass consistent with Hodgkin's involvement. A lymphangiogram showed right periaortic nodes to be abnormal. Between March 11 and April 4, 1969, the patient was treated with a cobaltous chloride Co 60 mantle and received 3,550 R at the sternal notch, and 3,340 R at the xiphoid process. During this initial therapy, her systemic symptoms cleared and the mediastinal mass regressed to the

Vascular Access for Cancer Chemotherapy

IN CERTAIN circumstances, vascular access for chronic intravenous chemotherapy in patients with malignant disease becomes difficult. Suitable superficial veins for the administration of chemotherapy occasionally become unavailable during the course of a prolonged regimen. The following case report illustrates an instance when a bovine heterograft arteriovenous fistula was used for repetitive chemotherapy in a patient with Hodgkin disease. <h3>Report of a Case</h3> A problem was recently encountered in finding venipuncture sites for the administration of intravenous medication to a 22-year-old girl suffering from nodular sclerosing Hodgkin disease. An attempt was made to administer chemotherapy, but superficial veins were impossible to find. It was decided to create a bovine graft arteriovenous fistula so that combination intravenous medication could be administered and the necessary blood samples for analysis drawn. On May 6,1974, a bovine heterograft arteriovenous fistula was created as a loop in her left arm. A 6.5-mm bovine graft was anastomosed

Complement receptor B lymphocytes in nodular sclerosing Hodgkin's disease

Infiltrated tissues from nine cases of nodular sclerosing Hodgkin's disease (NSHD) were examined for immunologic cell surface markers. In all nine cases a large population of complement receptor B-lymphocytes were present within the nodular infiltrates. B-lymphocytes were identified in frozen sections by adherence of sheep red blood cells (E) coated with IgM antibody (A) and complement (C) IgMEAC). IgMEAC attached to both small lymphocytes and to Reed-Sternberg cells and their variants. Red cells coated with IgG (IgGEA) attached to histiocytes associated with the internodular fibrous bands and only sparsely with the nodular infiltrates. The population of complement receptor lymphocytes appears to be an integral component of NSHD.