Nodular sclerosing Hodgkin's disease and large cell lymphoma. Immunophenotypic characterization of a composite case

Summary Composite lymphomas have rarely been reported in Hodgkin's disease (HD), except in the lymphocyte predominance sub-type, and immunohistochemical investigations have been performed in only few cases. We describe the histological and immunophenotypical findings in a case of composite nodular sclerosing HD and high-grade, large cell non-Hodgkin's lymphoma (NHL). In our case HD and NHL cells displayed striking morphological and immunophenotypical divergence, suggesting a lack of correlation between the two neoplasms.     

Expression of T-cell antigens on Reed-Sternberg cells in a subset of patients with nodular sclerosing and mixed cellularity Hodgkin's disease

Expression of T-cell antigens by Reed-Sternberg (RS) cells has not been detected in most studies of Hodgkin's disease (HD). The authors employed an improved method of fixation (paraformaldehyde-lysine-periodate), which sharply defined cell borders and revealed T-cell antigens on RS cells in 8 of 30 (27%) cases of HD. Antigen-specific staining was confirmed by immunoelectron microscopy. RS cells expressed T11 (8/8 cases), Leu-3 or T4 (4/8 cases), Leu-4 or T3 (3/8 cases), but not other T-cell specific antigens (Leu-1, T8, T6, 3A1). RS cells were negative for leukocyte common antigen (LCA/T200), in contrast to positive LCA/T200 staining of RS-like cells in T-cell lymphomas. RS cells in all HD cases were positive for Ki-1 and/or Leu-M1 antigens. The percentage of RS cells expressing T-cell antigens was less than 20% (2 cases), 20-50% (3 cases), or greater than 50% (3 cases). This percentage and the specific T-cell antigens expressed varied in tissues from different sites in each of 2 cases. Expression of T-cell antigens by RS cells was found in nodular sclerosis (6 of 20 cases) and mixed cellularity (2 of 5 cases) but not in lymphocyte predominance (2 cases), lymphocyte depletion (1 case), or unclassified types (2 cases). Two cases of nodular sclerosis contained areas of necrosis surrounded by sheets of lacunar cells (syncytial variant of NSHD). Two other cases were associated with cutaneous lymphoma. One of these cases was mixed cellularity HD, which appeared to be confined to the skin. In a second case, tumor cells of similar phenotype (T4+, Ki-1+) were found in skin and lymph nodes of a patient with coexistent mycosis fungoides and HD. These results are consistent with an origin of RS cells from T cells in some cases of nodular sclerosing and mixed cellularity HD. They also suggest that the same cell type, an activated helper T-cell, is involved in the pathogenesis of both skin lesions and lymphadenopathy of some patients with coexistent mycosis fungoides and HD.     

Phenotypic expression of Hodgkin''s and Reed-Sternberg cells in Hodgkin''s disease.

The phenotypic expression of Hodgkin's and Reed-Sternberg (H-RS) cells was determined by analysis with a panel of monoclonal antibodies and peanut agglutinin (PNA) by an immunohistochemical technique. Seven antibodies, including T200, anti-HLA-DR, anti-Leu 10, A1G3, anti-Tac, OKT9, and anti-Leu M1, were found to react with a great majority of H-RS cells. In some cases, H-RS cells also bound PNA. Other antibodies, including those highly specific for T cells (eg, Lyt 3) and B cells (eg, B1, anti-Leu 14) were consistently negative. The results argue against the derivation of H-RS cells from T or B lymphocytes. The H-RS cells were also negatively stained with antibodies which react with monocytes (OKM1, Mo-2, 63D-3), follicular dendritic cells (DRC-1), and natural killer/killer cells (Leu 7, Leu 11a, B73.1). The presence of Leu M1 and Tac in H-RS cells is of interest. Anti-Leu M1 positivity was seen in all 20 of Hodgkin's disease (HD) cases tested and should provide a very useful reagent for differential diagnosis of HD from other reactive and neoplastic conditions. Tac normally is present only on activated T cells. The presence of Tac in H-RS cells may reflect expression of T-cell growth factor receptor or a closely related protein during a stage of neoplastic transformation. Although the nature of the neoplastic cell of HD cannot be determined by these studies, they are consistent with an origin from interdigitating reticulum cells. Both H-RS cells and interdigitating reticulum cells have a similar antigenic phenotype (Leu M1+, T200+, HLA-DR+, Leu 10+, A1G3+, and OKT9+) and a similar pattern of lysosomal enzyme activity.     

Castleman's disease. Differences in follicular dendritic network in the hyaline vascular and plasma cell variants

Twenty-seven cases of the hyaline vascular variant and 10 cases of the plasma cell variant of Castleman's disease were studied with the paraffin resistant monoclonal antibodies Ki-FDC1p and/or Ki-M4p against follicular dendritic cells. Studies with the monoclonal antibody Ki-M9, for the detection of sinus lining cells, were also performed on the available frozen tissue in four cases of the hyaline vascular variant. In nine of the 10 plasma cell variant cases, the predominant type of follicular dendritic cell network was similar to that seen in normal or reactive germinal centres. In contrast, the hyaline vascular variant demonstrated either an expanded, disrupted, follicular dendritic cell network (10 cases) or multiple tight collections of follicular dendritic cells (16 cases). Sinus lining cells were not detected in the four cases studied. The difference in the predominant type of dendritic meshwork is an additional distinguishing feature to separate the plasma cell and hyaline vascular variants of Castleman's disease. The patterns of dendritic network seen in the hyaline vascular type, together with the absence of sinus lining cells, appear to favour the hamartoma theory proposed for this variant.     

Hodgkin''s disease, lymphocyte predominance type, nodular--further evidence for a B cell derivation. L & H variants of Reed-Sternberg cells express L26, a pan B cell marker.

Immunoreactivity for L26, a highly effective pan B cell marker that can be detected in paraffin sections, was evaluated in 72 cases of Hodgkin's disease of various histologic types. In all cases of nodular lymphocyte predominance type of Hodgkin's disease, L & H variants of Reed-Sternberg cells uniformly exhibited strong immunoreactivity for L26. Other variants of Reed-Sternberg cells, eg, lacunar, mononuclear, and diagnostic forms, present in nodular sclerosis, mixed cellularity, and lymphocyte depletion types of Hodgkin's disease, infrequently expressed L26 reactivity. In 55 of 63 cases (87%) of these combined types, less than 5% of Reed-Sternberg cells or variants were L26 positive. In the remaining cases, a larger proportion of these cells expressed L26. Topographic patterns of immunoreactivity for small lymphocytes in these different types of Hodgkin's disease also varied. In nodular lymphocyte predominance type, L26 positive lymphocytes (presumptive B cells) were mainly localized to nodular areas of the proliferation. In other types of Hodgkin's disease, L26 positive cells occurred in small or large aggregates and generally represented a minor proportion of the population of lymphoid cells. These studies further support a B cell derivation for L & H variants of Reed-Sternberg cells and provide additional evidence that nodular lymphocyte predominance type Hodgkin's disease may represent a distinct entity, possibly an unusual low grade B cell lymphoma. These data also suggest that some Reed-Sternberg cells and variants present in other histologic types of Hodgkin's disease may be of B cell derivation, and precludes the use of L26 as a diagnostic discriminant in cases in which the distinction between Hodgkin's disease and non-Hodgkin's lymphoma is unclear.     

Immunological capacity of lymphocytes from untreated patients with Hodgkin''s disease evaluated in mixed lymphocyte culture.

Blood lymphocytes from thirty-nine untreated patients with Hodgkin's disease were tested for stimulatory and responding capacity in mixed lymphocyte culture. The response to allogeneic lymphocytes was impaired in ten patients but the mean response of the patient group did not differ from healthy controls. Lymphocytes from female patients responded better than male patients (P less than 0-02). The stimulatory efficacy was severely impaired in patients' lymphocytes (P less than 0-001). Age, clinical stage and histopathology had no significant influence on the responding or stimulatory capacity.     

Recent advances in mastocytosis and neoplasms of probable monocytic/dendritic cell lineage

In recent years, there has been a better appreciation of mast cell and monocyte/macrophage/histiocyte/dendritic cell ontogeny, which has led to reclassification of certain entities within the World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues. Notably, mastocytosis has been reclassified as a chronic myeloproliferative neoplasm, while the former “blastic natural killer cell lymphoma” or “haematodermic neoplasm” is now known as a blastic plasmacytoid dendritic cell neoplasm and classified with the acute leukaemias. This review aims to give a brief overview of the physiological roles and patterns of migration of the corresponding normal cells before discussing the presentation and diagnostic features of mast cell and monocyte/dendritic cell neoplasms. Distinguishing reactive from neoplastic proliferations still poses major challenges and the reasons for this are briefly explained.     

Reticulum cell sarcoma of lymph node with mixed dendritic and fibroblastic features.

We report a case of clinically aggressive reticulum cell sarcoma with mixed follicular dendritic cell (FDC) and fibroblastic reticular cell (FRC) features. Histologically, the tumor was confined to lymph nodes occurring as a multifocal epithelioid and spindle cell proliferation with appreciable mitotic rate and numerous admixed non-neoplastic B-cells. Ultrastructural examination revealed elongated cells with prominent nucleoli, interdigitating cell processes and frequent desmosomes. These features are typical of FDC sarcoma. However, immunohistochemical stains showed no expression of antigens characteristic of FDCs, including CD21, CD23 and CD35. Cytogenetic characterization of this tumor, by conventional G-banding and multicolor spectral karyotyping, revealed multiple clonal chromosomal aberrations, including del(X)(p11.4) and add (21)(p11.2). Gene expression analysis by cDNA microarray of RNA obtained from short-term tumor cultures revealed high-level expression of a set of genes (including PDGF receptor-alpha and -beta, certain metalloproteinases, and CD105) that were also highly expressed in cultures of nodal FRC cultured from non-neoplastic lymph nodes. We propose that this tumor represents a nodal sarcoma with intermediate differentiation between FDCs and FRCs. This case adds to the diversity of tumors that may arise from lymph node stroma and supports a possible relationship between the FDC and FRC lineages.     

Paraffin section immunohistochemistry. II. Hodgkin''s disease and large cell anaplastic (Ki1) lymphoma

A panel of antibodies that recognize antigens that survive fixation and conventional processing have been applied to 43 cases of Hodgkin's disease and five cases of large cell anaplastic lymphoma. Reed-Sternberg cells in all five cases of nodular lymphocyte predominance Hodgkin's disease were positive with leucocyte common (CD45) and B-cell antibodies, and negative with LeuM1 (CD15) and BerH2 (CD30) antibodies. In other types of Hodgkin's disease, Reed-Sternberg cells were positive with BerH2 in all cases, positive with LeuM1 in 63% of cases (with enzymic predigestion), positive with at least one B-cell antibody in 29% of cases and positive for CD45 in 8% of cases. In 19% of all cases, Reed-Sternberg cells were positive for epithelial membrane antigen and in 93% they were positive with TAL1B5 (anti-class II MHC). No case showed immunoreactivity with anti-T-cell antibodies. The patterns of immunoreactivity of large cell anaplastic lymphoma were similar, except that none was positive with B-cell antibodies and three were positive with T-cell antibodies. All five were positive with BerH2 (CD30) and TAL1B5. Comparison of the results with those seen in other cases of non-Hodgkin's lymphoma indicates that, with the currently available reagents, this immunohistological profile cannot be used as the sole diagnostic discriminant of these conditions; this must still be based upon careful morphological assessment.     

Rearrangement of immunoglobulin and T-cell receptor genes in Hodgkin''s disease.

The precise cellular origin of the malignant cell population in Hodgkin's disease (HD) is unknown. Recent application of Southern blotting techniques to detect clonal rearrangements of immunoglobulin (Ig) and T-cell receptor (TCR) genes has yielded conflicting results. The authors report the detailed analysis of tumor tissue DNA obtained from 18 cases of HD using Ig and TCR gene probes. The distribution of HD subtypes was similar to that in other series. Samples were examined for rearrangement by means of multiple restriction enzymes with specific probes for the Ig heavy chain, Ig kappa, Ig lambda, TCR beta, and TCR gamma loci. Only germline bands were detected in all 18 cases with the Ig gene probes and in 15 of 18 cases with the TCR probes. In 2 cases blot analysis suggested a predominance of polyclonal (or oligoclonal) T cells. In 1 case monoclonal rearrangement of the TCR beta gene was detected. Based on the intensity of the rearrangement and the small percentage of Reed-Sternberg (R-S) cells in this case, the clonal population detected was most likely not the R-S cell itself. The data do not support the frequent occurrence of Ig or TCR monoclonal gene rearrangement in HD.     

经典型滤泡树突细胞肉瘤的特殊变异形态及潜在诊断陷阱

目的探讨经典型滤泡树突细胞肉瘤(FDCS)的临床病理特征、特殊变异形态及潜在诊断陷阱,提高诊断准确性。方法对2006—2018年陆军军医大学第一附属医院诊断的25例经典型FDCS进行组织形态观察、免疫组织化学染色和EB病毒编码的小RNA(EBER)原位杂交检测,结合文献分析其特殊变异形态的类型和特点。结果25例FDCS患者年龄23~77岁(平均52岁),男女比例为1.5∶1.0,肿瘤最大径1.5~20.0 cm(平均7.4 cm),其中12例(48%)在初次诊断时被误诊。17例有随访信息,随访时间5~96个月,复发、转移、病死比例分别为3/17、5/17、2/17。除了典型组织形态外,10例FDCS可见特殊的变异形态和/或组织结构,包括淋巴上皮癌样、促结缔组织增生性浸润癌样、霍奇金淋巴瘤样、间变性大细胞淋巴瘤样及血管外皮细胞瘤样等,是需要重视的潜在诊断陷阱。免疫组织化学染色结果显示典型形态和各种特殊的变异形态均可表达2个以上滤泡树突细胞标志物(CD21、CD23、CD35等)。EBER原位杂交检测显示25例FDCS均为阴性。结论经典型FDCS罕见,除了典型的组织形态外还可出现多种特殊的变异形态,其中鼻咽部的淋巴上皮癌样、纵隔或淋巴结内的霍奇金淋巴瘤样、间变性大细胞淋巴瘤样变异型尤其值得我们重视。加强对此类罕见变异形态的认识,提高诊断警惕性,有助于避免误诊。     

Increased luminol-enhanced chemiluminescence of blood monocytes and granulocytes in Hodgkin''s disease.

The oxidative metabolic burst of blood monocytes and polymorphonuclear leukocytes (PMN) from 22 untreated patients with Hodgkin's disease (HD) and 18 healthy subjects were studied. Monocytes and PMN were enriched by density centrifugation and in vitro activated by zymosan. The oxidative metabolism was measured by luminol-enhanced chemiluminescence (CL). The CL of the patients' monocytes and PMN was higher than that of controls (P less than 0.01 and P less than 0.05, respectively). Patients with stage II-IV HD showed an increased blood monocyte CL as compared with stage I patients (P less than 0.05). Furthermore, patients with lymphocytic depletion or mixed cellularity subtype demonstrated an increased CL of PMN as compared with the remainder. Enhanced CL of phagocytes has been observed in chronic inflammatory disease and can be induced by various serum factors such as monokines and immune complexes. The present study demonstrates an increased CL of blood-borne phagocytic cells in untreated HD. Furthermore, CL of blood monocytes and PMN correlated to tumour burden and histologic subtype, respectively.     

HIV-infected cells are major inducers of plasmacytoid dendritic cell interferon production, maturation, and migration

Plasmacytoid dendritic cells (PDC), natural type-1 interferon (IFN) producing cells, could play a role in the innate anti-HIV immune response. Previous reports indicated that PDC IFN production is induced by HIV. Our results show a more robust IFN induction when purified PDC (>95%) were exposed to HIV-infected cells. This effect was not observed with non-viable cells, DNA, and RNA extracted from infected cells, and viral proteins. The response was blocked by anti-CD4 and neutralizing anti-gp120 antibodies as well as soluble CD4. IFN induction by HIV-infected cells was also prevented by low-dose chloroquine, which inhibits endosomal acidification. PDC IFN release resulted in reduced HIV production by infected CD4+ cells, supporting an anti-HIV activity of PDC. Stimulated CD4+ cells induced PDC activation and maturation; markers for PDC migration (CCR7) were enhanced by HIV-infected CD4+ cells only. This latter finding could explain the decline in circulating PDC in HIV-infected individuals.     

Eosinophils are the major source of transforming growth factor-beta 1 in nodular sclerosing Hodgkin's disease.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine which promotes fibroblast growth and collagen synthesis, but suppresses growth and differentiation of immune lymphocytes and killer cells. Immunohistochemical detection of TGF-beta 1 in Hodgkin's disease (HD) has been shown to correlate with the histologic feature of nodular sclerosis, which is associated with a favorable prognosis (American Journal of Pathology 1990, 136:1209). In that study, TGF-beta 1 was localized mainly at the margins of broad collagen bands (presumably sites of new collagen synthesis) and in areas containing numerous Hodgkin/Reed-Sternberg cells (H/RS). In these areas, TGF-beta 1 protein was found on the membrane and occasionally within the cytoplasm of H/RS cells. To determine whether TGF-beta 1 is synthesized by H/RS cells or secondarily bound to their membrane and sometimes internalized, we performed in situ hybridization (ISH) using 1.5 Kb 35S-labeled anti-sense and sense RNA probes to TGF-beta 1. Paraffin-embedded tissues of 10 cases from all histologic types of HD were examined. Somewhat unexpectedly, the major site of TGF-beta 1 mRNA was in eosinophils; TGF-beta 1 mRNA was not detected in H/RS cells. TGF-beta 1 mRNA was found in eosinophils in all cases of nodular sclerosis but not in other types of HD, despite the presence of numerous eosinophils in mixed cellularity cases. The presence of TGF-beta 1 mRNA coincided with immunohistochemical detection of TGF-beta 1 protein using antibody CC (1-30). These results confirm the role of TGF-beta 1 in the histogenesis of nodular sclerosing HD and indicate that eosinophils are the major source of TGF-beta 1 in this type of HD.     

Immunological properties of thymus cell subpopulations: rat thymic dendritic cells are potent accessory cells and stimulators in a mixed leukocyte culture

Rat thymus cells were fractionated by centrifugation on a discontinuous bovine serum albumin gradient into two subpopulations: one of high density that accounted for>90% of the recovered cells, and a minor low-density subpopulation containing 4 to 10% of the total cells. The high-density subpopulation consisted mainly of uniform small-sized thymocyteS, whereas the low-density subpopulation contained mostly larger-sized cells. High-density thymus cells did not function either as stimulators in a mixed leukocyte reaction or as accessory cells required for T-cell response to mitogens, Con A and sodium periodate, as determined by ³H-thymidine incorporation. Dense thymus cells also responded poorly to allogeneic and to mitogenic stimulation, even when accessory cells were added. In contrast, the low-density thymus cells responded well to allogeneic stimulation and to both mitogens. In addition, low-density thymus cells possessed stimulatory activity in mixed leukocyte cultures, as well as accessory activity for mitogenic responses. Both activities were found to reside in dendritic cells that were purified extensively (70-90% of the preparation) with good yield. When tested as accessory cells for T-cell responses to periodate, thymic dendritic cells were as potent as lymph node dendritic cells on a per cell basis. A small number of thymic dendritic cells was able to cause marked enhancement in T-lymphocyte proliferation in response to stimulation. By immunofluorescence thymic dendritic cells were shown to be Ia-positive, but Thy 1.1-negative.     

Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen-presenting cells.

Immune surveillance of skin cancer involves the stimulation of effector T cells by tumor-derived antigens and antigen-presenting cells (APCs). An effective APC must not only display processed antigen in the context of MHC molecules but also express co-stimulatory molecules that are required to fully activate T cells. One of the most common cutaneous neoplasms is basal cell carcinoma. To investigate expression of the co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) on tumor-associated dendritic cells (TADCs), cryosections from basal cell carcinomas were immunostained. In basal cell carcinomas, only 1 to 2% of intratumor and 5 to 10% of peritumor APCs expressed CD80 or CD86. In contrast, biopsies of immunological/inflammatory dermatoses revealed that 38 to 73% of APCs expressed CD80 and CD86. To further evaluate their phenotype and function, TADCs were isolated from tissue samples of basal cell carcinomas; they were non-adherent to plastic, displayed a typical dendritic morphology, and expressed high levels of major histocompatibility class II molecules on their surface. When TADCs were compared with dendritic cells from blood for presentation of superantigens (staphylococcal enterotoxins A and B) to resting autologous T cells, TADCs were consistently weaker stimulators of T cell proliferation than blood dendritic cells. When analyzed by flow cytometry, TADCs expressed high levels of HLA-DR, but only 5 to 10% co-expressed CD80 or CD86. A 3-day culture in granulocyte/macrophage colony-stimulating factor-containing medium partially reconstituted the TADC expression of CD80 and CD86 as well as their immunostimulatory capacity. Thus, in this common skin cancer, although there are prominent collections of HLA-DR-positive APCs in and around tumor cells, the TADCs are deficient in important co-stimulatory molecules as well as being weak stimulators of T cell proliferation. The paucity of co-stimulatory molecule expression and functional activity of TADCs may explain why the local T lymphocytic infiltrate fails to become fully activated to eradicate adjacent tumor cells. From a clinical perspective, these findings suggest a novel immunotherapeutic strategy targeting T cell co-stimulatory molecules on professional APCs in cutaneous oncology.     

Surface markers and cytotoxic activity of blood natural killer cells studied at the single cell level in Hodgkin''s disease.

Purified peripheral blood lymphocytes (PBL) from nine untreated patients with Hodgkin's disease (HD), two HD patients in complete remission and 17 healthy donors were studied for natural killer (NK) cell activity against the K-562 cell line using a single cell cytotoxic assay, which allowed enumeration of effector cells and characterization of their surface membrane phenotypes after staining with monoclonal antibodies. The frequency of NK cells was significantly lower in HD patients than in controls (mean % +/- s.d., 1.9 +/- 0.9 and 2.8 +/- 1.2, respectively), while the fraction of target binding cells was similar in the two groups. The fraction of cytotoxic lymphocytes increased after pre-treatment of PBL with 500 iu leucocyte interferon in all tested control donors (n = 12) and the two patients in remission but only in four of seven untreated patients. No relation between the impaired NK cell frequency and age, tumour histology and clinical stage could be revealed. Subtyping of the target cell binding NK cells by monoclonal antibodies disclosed a marked heterogeneity of effector cells. NK effector cells reactive with M1 and anti-Ia antibodies were enriched while T3+ and T4+ NK lymphocytes tended to be reduced as compared to PBL. There was no difference between patients and healthy donors with regard to the surface antigen patterns of NK cells. Interferon treatment did not alter significantly the phenotypic characteristics of cytotoxic lymphocytes in patients and controls. It is concluded that the impairment of NK cell activity in HD is partly attributed to a lower frequency of cytotoxic effector cells among a normal number of target binding cells. The defect could not be attributed to a selective defect of effector cell subsets.     

Granulocyte and HLA-D region specific monoclonal antibodies in the diagnosis of Hodgkin''s disease.

Tissue sections embedded in paraffin and fixed in formalin from 32 patients with Hodgkin's disease, representing the major histological subtypes, were studied using two granulocyte specific monoclonal antibodies (Leu-M1 and 3C4) and an HLA-D region specific monoclonal antibody (TAL-IB5). Reed-Sternberg cells were stained with one or other of the antigranulocyte antibodies in the nodular sclerosing and lymphocyte depleted subtypes. Reed-Sternberg cells in all but three cases of mixed cellularity Hodgkin's disease were positive with both Leu-M1 and 3C4. One case stained with only Leu-M1, and two cases were consistently negative with both antibodies. HLA-DR was widely expressed in the Reed-Sternberg cells of all three subtypes. In the four cases of lymphocyte predominant Hodgkin's disease the multinucleated Reed-Sternberg cells did not stain with either antigranulocyte antibody but were strongly positive with anti-HLA-DR. Twenty five cases of non-Hodgkin's lymphoma, in which there were multinucleated giant cells resembling Reed-Sternberg cells, were studied in a similar way. These cases included pleomorphic T cell and B cell lymphomas, histiocytic lymphomas, and malignant histiocytosis of the intestine. In none of these did the multinucleated cells stain with either antigranulocyte antibody, but in most cases the multinucleated cells stained with anti-HLA-DR. In two cases of the tumour stage of mycosis fungoides dot like intracytoplasmic staining was shown in the tumour cells with both antigranulocyte markers. The monoclonal antigranulocyte antibodies Leu-M1 and 3C4 are of considerable value in both the diagnosis and the differential diagnosis of Hodgkin's disease and are particularly valuable in that they can be applied to tissue fixed in formalin and embedded in paraffin. Antibody to HLA-DR, while useful, is of less value.     

Ecotaxis: the principle and its application to the study of Hodgkin''s disease.

A study of the function, characterization and distribution of T and B lymphocytes in five children with Hodgkin's disease is presented. The results, indicating that lymphocyte depletion in the peripheral blood does not necessarily reflect an overall lack of circulating lymphocytes, are presented to demonstrate that failure of ecotaxis (normal lymphocyte migration and distribution) can occur in man. The underlying reasons for such failure and their relevance to the pathogenesis of Hodgkin's disease are discussed.