Pulmonary Hodgkin's disease. Diagnosis by fine needle aspiration

The cytologic manifestations of pulmonary Hodgkin's disease in transthoracic fine needle aspirates from 13 patients with pulmonary radiologic abnormalities and a previous diagnosis of Hodgkin's disease are described. Classic Reed-Sternberg cells and lacunar cells were present in most cases. The so-called "mononuclear" Reed-Sternberg cells were identified in all cases. A cellular background consisting of variable numbers of histiocytes, eosinophilic and neutrophilic leukocytes and lymphocytes was frequently present. Such a background should stimulate a search for cells diagnostic of Hodgkin's disease. We conclude that the cytologic features of Hodgkin's disease are not only characteristic, but are also diagnostic, in patients with a prior history of Hodgkin's disease in whom pulmonary recurrence is suspected.     

Hodgkin's disease; a clinical-pathological review of 150 cases

One hundred and fifty cases of Hodgkin's disease were analyzed in an effort to detect significant clinical-pathological correlations and to elucidate any possible factors of prognostic or etiological importance.A relatively long survival for patients with Hodgkin's paragranuloma was not noted in this series. Instead the survival rate among them was closely parallel to that of patients with classical granuloma. Hodgkin's sarcoma is a more malignant disease with a patient survival rate not more than half that of patients with the granuloma variety. It is not necessarily a disease of older age groups. Great caution must be exercised to avoid including non-Hodgkin's disease tumors under the heading of Hodgkin's sarcoma or paragranuloma. The series reported corresponds with many other reported series of Hodgkin's disease as regards greater incidence in males and longer survival in females. In this series the cases in patients under the age of 15 were all in males. The predominance of initial enlargement of the cervical nodes was again noted in this series, as was the high proportion of negative reaction to tuberculin tests. The incidence of tuberculous lesions in patients who died of Hodgkin's disease was only slightly greater than in those who died of other lymphoma. Site of origin of the disease apparently affects survival time. There was statistical evidence that gonadal activity might influence the equilibrium of the disease. Lymph node bacteriological cultures were not remarkable. Brucella organisms were absent. Fertile egg passages for detecting possible viral agents revealed increased egg mortality and cutaneous sensitivity reactions to the harvested amniotic fluid.     

Lymphocyte populations of non-scleronodular Hodgkin's disease subtypes in different stages of lymphocyte depletion. An immunophenotypic and quantitative study

Twenty-one cases of non-scleronodular Hodgkin's disease with variable lymphocyte contents were studied immunophenotypically and quantitatively to analyse the distribution of different lymphocyte populations and to determine whether selective loss of lymphocyte subpopulations accompanies overall lymphocyte depletion. In Hodgkin's tissue B-cells were scanty and unevenly distributed in samples with both many and few lymphocytes. Several large B, LN1-positive (possibly activated) cells were observed in a few cases. CD3-positive T-lymphocytes predominated in all cases; the same cells were also UCHL1-positive, thus expressing characteristics of mature T-memory cells. CD4-positive lymphocytes were usually more numerous than CD8-positive lymphocytes, but quantitative evaluation of the latter showed that they did not decrease in proportion to any diminution of the whole lymphocyte population. This finding suggests that in the process of lymphocyte depletion more CD4-positive lymphocytes than CD8-positive lymphocytes are lost, and this might account for the impairment of cell-mediated immunity in Hodgkin's disease.     

In situ quantification of T-cell subsets, NK-like cells and macrophages in Hodgkin's disease: quantity and quality of infiltration density depends on histopathological subtypes

The present investigation addressed itself to the in situ quantification of reactive cells in tumour tissues affected by Hodgkin's disease. Immunostaining was used for identification and stereology was used for enumeration of T-helper/inducer (CD4+) T-cytotoxic/suppressor (CD8+), NK-like (Leu7+) and cells of macrophage origin (Mono 2+). The evaluation of 50 cases showed that CD4+ cells always outnumbered CD8+ cells but the degree of this predominance varied depending on the histopathological subtypes (n.s. greater than m.c. greater than l.d.). Lymph nodes contained more CD4+ as well as CD8+ cells compared to spleens. Therefore, no changes in the T4:T8 ratio occurred. No significant differences in the densities of NK-like cells were observed, comparing the different histopathological subtypes as well as lymph nodes and spleens. Similarly, macrophage (M phi) density was comparable in all histopathological subtypes. However, lymph nodes contained significantly more M phi compared to spleens. On comparison of reactive cells in Hodgkin's tissues to non-Hodgkin lymphomas (79 cases) and normal controls (7 cases) significantly higher numbers of CD4+, CD8+ and Mono 2+ cells were found in Hodgkin's compared to non-Hodgkin's lymphomas. In contrast, the density of NK-like cells in NHL as well as in normal tissues was fivefold compared to that observed in Hodgkin's tissues.     

Chronic lymphocytic leukemia and Hodgkin's disease in the same patient: a report of two cases

Two cases with coexistent chronic lymphocytic leukemia and Hodgkin's disease are reported. The first appeared disease was the chronic lymphocytic leukemia. The eventual influence of this disease on the development of the Hodgkin's disease is discussed.     

Lipid changes occuring in the course of hematological cancers

The relationship between plasma lipid levels and mortality from cardiovascular diseases has been shown in many studies, but there has been far less investigation into their relationship to non-cardiovascular diseases. The aim of this study was to investigate the lipid profile of individuals with hematological malignancies and its relationship to disease activity. 238 patients were included in the study: 84 with acute leukemia, 62 with non-Hodgkin lymphoma, 35 with Hodgkin's lymphoma, 32 with multiple myeloma, and 25 with myeloproliferative syndrome. The HDL cholesterol level of the patients differed to that of the individuals in the control group in the active disease period for all the analyzed disorders, but only remained statistically significant in the acute leukemia and non-Hodgkin lymphoma groups during the remission period. Smaller differences were observed for the remaining lipid fractions, except for the triglyceride level, which increased in the active disease period in all the analyzed disorders except non-Hodgkin lymphoma. The most pronounced changes in the lipid fractions occurred in the HDL cholesterol level, and were the most remarkable for acute leukemia.     

INFRACLAVICULAR CHEST WALL TUMORS IN HODGKIN'S DISEASE

In six of 91 cases of Hodgkin''s disease observed over a three-year period, a tumor mass filling the infraclavicular hollow was noted. It was on the left side in all instances. Although in four cases it was the only superficial manifestation of Hodgkin''s disease for a long period, in all cases there were ultimately other areas of involvement. The lesion did not occur in any of 81 cases of lymphosarcoma observed concurrently.     

Production and characterization of a monoclonal antibody that binds Reed-Sternberg cells

A murine monoclonal antibody, termed HeFi-1, was produced after immunization with the L428 Hodgkin's disease tissue culture cell line. HeFi-1 selectively stained only the Reed-Sternberg or Hodgkin's cells in 18 of 18 cases of Hodgkin's disease, including the nodular sclerosis, mixed cellularity, and lymphocyte-depleted histologic subtypes. HeFi-1 did not stain any cells in normal lung, brain, salivary gland, thyroid, gall bladder, pancreas, liver, testis, breast, endometrium, or kidney. Rare large cells at the edge of the lymphoid follicles were stained in normal tonsil, colon, and hyperplastic thymus. There was no staining of any cells in 14 cases of B cell non-Hodgkin's lymphoma; however, the malignant cells in three of 11 cases of non-Hodgkin's lymphoma which appeared to express T cell markers were also stained with HeFi-1. Tissue culture cell lines including the T cell acute lymphocytic leukemia lines MOLT4 and CEM, the histiocytic cell line U-937, and the amniotic cell line WISH were not stained. Seven Epstein Barr virus (EBV)-positive lymphoblastoid cell lines were stained with HeFi-1, but there was no staining of three EBV+ African Burkitt's lymphoma cell lines or three EBV- American Burkitt's cell lines. HeFi-1 did not block the ability of the L428 cells to stimulate a mixed lymphocyte reaction or function as accessory cells for mitogen-induced human T cell proliferative responses. Modulation of the HeFi-1 cell surface antigen on the L428 cells was not observed. HeFi-1 specifically immunoprecipitated a cell surface protein of approximately 120,000 daltons from both the L428 and EBV+ lymphoblastoid cell lines. HeFi-1 monoclonal antibody should prove useful not only in the diagnosis, staging, and potential therapy of Hodgkin's disease, but also for determining the cell of origin of the Reed-Sternberg cell.     

Chromosome abnormalities in peripheral blood lymphocytes from untreated Hodgkin's patients

Summary We describe the presence of a high frequency of spontaneous chromosome aberrations in lymphocytes from six untreated patients with Hodgkin's disease. The characteristics of the chromosome abnormalities observed suggest the existence of a certain degree of chromosome instability in these cases, that could be a predisposing factor for the development of malignancies.     

Prognostic role of natural killer cells in pediatric mixed cellularity and nodular sclerosing Hodgkin's disease

OBJECTIVE: To study natural killer cells' spontaneous cytotoxic capacity against tumor cells and their prognostic significance in classical Hodgkin's disease. STUDY DESIGN: Thirty-eight pediatric mixed cellularity and nodular sclerosing Hodgkin's disease patients were included in the study. Immunohistochemical staining was performed for natural killer cells in the background using the monoclonal antibody CD57 in serial sections of B5-formalin-fixed, paraffin-embedded tissue blocks. CD57-positive cells were counted with an immersion objective among 5,000 cells on representative areas of the tumors. The degree of natural killer cells was classified as low (<150 cells) or high (> or = 150 cells). Multivariate regression analysis was performed to determine the differences between patients with and without relapse. RESULT: The mean of CD57-positive cell numberfor all the cases was 173.42 +/- 117.34 (range, 20-500). CD57-positive cells were high in 21 cases and low in 17. The mean of CD57-positive cell numbers was 191.85 +/- 115.33 in the disease-free group and 84.44 +/- 57.90 in the relapsing group. Log rank analysis showed statistical significance between event-free survival and number of CD57-positive cells (P = .0207). CONCLUSION: In multivariate analysis, CD57 expression proved to be a prognostic factor independent from otherfactors. As a result, CD57 expression by background natural killer cells may be used as a prognostic parameter in mixed cellularity and nodular sclerosing Hodgkin's disease.     

An unusual presentation of fine needle aspiration (FNA) cytology from the syncytial variant of nodular sclerosing Hodgkin's disease

Introduction
Open access breast clinics are now widely available and immediate reporting of FNAs of the breast has become an established part of the triple approach to the management of breast disease ¹ .
We report the unexpected findings of a case of Hodgkin's disease at such a clinic. The patient was a young woman who initially was thought by both her general practitioner and surgeon to have a fibroadenoma in the axillary tail region of her right breast. The FNA of this lump showed the features of Hodgkin's disease but with widespread necrosis, which was unusual and potentially misleading and which we wish to highlight. A lymph node biopsy confirmed the diagnosis and showed that the patient was suffering from the syncytial variant of nodular sclerosing Hodgkin's disease (NSHD).
This variant probably accounts for about 5% of cases of Hodgkin's disease ² . Necrosis is a common feature of NSHD; it can range from minute scattered foci to more extensive necrosis of nodules or even involve the entire lymph node.     

Immunoenzymatic assessment of interferon-gamma in Hodgkin and Sternberg-Reed cells

The typical histological picture seen in Hodgkin's disease is consistent with the release of cytokines and other active mediators by the malignant cells, i.e., Hodgkin and Sternberg-Reed cells. Since interferon-gamma is regarded as an important regulator of the cytokine cascade, we have undertaken an immunohistological assessment of this mediator in Hodgkin's disease tissue biopsies. In approximately 50% of the cases investigated we found Hodgkin and Sternberg-Reed cells to be positive with antibodies against interferon-gamma. These in situ findings were substantiated by immunostaining of Hodgkin's disease-derived cell lines L428 and L540. L540 was consistently positive, whereas L428 was negative. It is noteworthy that L428 exhibit a B-cell pheno- and genotype, whereas L540 is of T-cell origin. These data are consistent with theories that propose that cytokine production by tumour cells is central to the pathogenesis of Hodgkin's lymphoma.     

Molecular genetic analysis in the diagnosis of lymphoma in fine needle aspiration biopsies. II. Lymphomas versus nonlymphoid malignant tumors

The configurations of immunoglobulin genes and T-cell receptor beta chain genes were analyzed by Southern blotting in DNA derived from nonlymphoid malignant tumors and lymphomas. Gene rearrangements were not detected in any of the 35 cases of nonlymphoid malignant tumors. On the contrary, they were shown in all 14 cases of non-Hodgkin's lymphomas, 2 of 3 cases of Hodgkin's disease and 2 cases diagnosed as non-Hodgkin's lymphoma or angioimmunoblastic lymphadenopathy. The differentiation by light microscopy between lymphoma and nonlymphoid malignant tumors was a diagnostic problem in five cases; the molecular genetic analysis of DNA was contributory in all five diagnostically difficult aspirates. By gene rearrangement studies, the diagnosis of lymphoma was confirmed in two cases and nonlymphoid malignant tumors were accurately indicated in aspirates diagnosed finally as rhabdomyosarcoma (one case) and carcinoma (two cases).     

Cytodiagnosis of Hodgkin's disease in sputum specimens

In patients with histologically proven Hodgkin's disease, knowledge of the extent of involvement of lymph nodes and other organs has proven valuable in the determination of treatment and prognosis. One of the most common sites of involvement outside the hematopoietic system has been shown to be the lung parenchyma; in this study, six patients with a tissue-proven diagnosis of Hogdkin's disease and positive cytologic findings in the sputum were reviewed. Three cell types not found in normal sputum specimens were identified in these patients and were correlated with the histologic patterns of the tumors as seen in lung biopsies. Our results suggest the usefulness of sputum examination as an adjunctive or possibly a substitute diagnostic procedure in the evaluation of patients with Hodgkin's disease and possible lung involvement. They also suggest that in some cases the cytologic diagnosis can be quite specific in the identification of neoplastic cells as consistent with a diagnosis of Hodgkin's disease.     

L-428 Reed-Sternberg cells and mononuclear Hodgkin's cells arise from a single cloned mononuclear cell

The L-428 cell line derived from nodular sclerosing Hodgkin's disease was verified to be a human female cell line with surface marker and morphologic characteristics similar to native Hodgkin's cells. Single cells were cloned and subcloned twice to determine the characteristics of the clonogenic L-428 Hodgkin's cell (resulting in a 10% cloning efficiency). Both mononuclear L-428 cells and classical Reed-Sternberg cells arose from solitary cells. The clonogenic cell was the mononuclear Hodgkin's cell, although small abortive colonies sometimes arose from classical binucleate Reed-Sternberg cells. Cytogenetic and phenotypic analysis supported the clonality of three subclones and indicated, among many findings, consistent abnormalities of the long arm of chromosome 7 (beta-chain of the T cell receptor) and 14q32 (Ig heavy chain). Distinctive abnormalities of cytogenetics, phenotyping and transforming growth factor-beta production were exhibited for each clone as well. These observations demonstrate the relationship of the continuum of malignant mononuclear and multinuclear Reed-Sternberg cells in this cell culture from nodular sclerosing Hodgkin's disease and suggest that a similar relationship exists in native Hodgkin's disease tissue. These observations also support the theory of clonality in Hodgkin's disease and suggest that in vivo contiguous metastasis in the L-428 Hodgkin's disease patient was most likely accomplished by a Ki-1 positive small mononuclear cell.     

The value of lymph node imprint cytodiagnosis: an assessment of interobserver agreement and diagnostic accuracy

The value of lymph node imprint cytodiagnosis: an assessment of interobserver agreement and diagnostic accuracy
The aim of this study was to assess the reliability of cytodiagnosis of lymph node imprints without fixed tissue sections. One hundred randomly selected archival cases were used in the study. These air‐dried May–Grünwald–Giemsa imprint slides were assessed independently and blind by three pathologists. Cases were assigned to one of four diagnostic categories: reactive changes, non‐Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and secondary malignancy. Each broad diagnosis was compared with the 'correct' reviewed histological diagnosis to calculate interobserver agreement and diagnostic accuracy. The overall κ score (+0.59) was indicative of moderate agreement. The mean pathologist diagnostic accuracy was 78%, with complete agreement with the histological diagnosis in 61% of cases. The main diagnostic difficulties were in the distinction between reactive changes and NHL and distinguishing NHL from HD. Further diagnostic classification, e.g. typing of lymphomas and subclassification of Hodgkin's disease, was not found to be reliable using the imprints alone. With these limitations in mind, pathologists should be able to use lymph node imprints for cytodiagnosis in selected cases. The study also emphasized the utility of imprints as a corollary to the histology and as a tool for cytology training and continuing education.     

Value of fine needle aspiration cytology in the initial diagnosis of Hodgkin's disease. Analysis of 188 cases with an emphasis on diagnostic pitfalls

OBJECTIVE: To evaluate the diagnostic accuracy and pitfalls of fine needle aspiration (FNA) cytology in the initial evaluation of Hodgkin's disease (HD) and to assess the influence of the pathologist's experience by comparing the results during two periods. STUDY DESIGN: A total of 170 cytodiagnoses of HD were reviewed and compared with those on the final histopathologic report. Thirty-three cases of HD with a previous, different cytologic diagnosis were also selected. In all the cases under study, FNA was performed as part of the initial diagnostic approach. From a practical perspective, diagnostic errors were divided into major or minor according to the consequences on patient management. RESULTS: Fifteen cytologic diagnoses of HD were followed by a different histologic diagnosis after lymph node biopsy. In 33 cases of HD an erroneous cytologic diagnosis was given prior to biopsy. The sensitivity of the series was 82.4% (86.1% excluding nonrepresentative cases). The positive predictive value reached 91.2%. Sensitivity varied from 79.3% in the first period (1982-1990) to 84.9% in the second (1991-1999) (83.3% and 88.2%, respectively, excluding nonrepresentative cases). Similarly, the positive predictive value increased from 89% to 92.8%. Diagnostic errors with important consequences for patient management diminished from 14 in the first period to 5 in the second. CONCLUSION: Cytology offers a rapid and accurate approach not only for the diagnosis of recurrent HD but also for its initial recognition. These results increase the capacity of FNA as a first-level diagnostic technique in the screening of lymphadenopathies.     

Fine needle aspiration cytology diagnosis of lymphoproliferative disease of the breast

OBJECTIVE: To evaluate the role of fine needle aspiration cytology (FNAC) in the diagnosis of lymphoproliferative disease (LPD) of the breast. STUDY DESIGN: Over a period of 20 years (January 1982-December 2001), 13 diagnosed and/or suspected cases of LPD of the breast on FNAC were retrieved and reviewed from the files of the Cytology Laboratory, Department of Pathology, All India Institute of Medical Sciences. For each case, both May-Grünwald-Giemsa- and Papanicolaou-stained smears were reviewed along with hematoxylin and eosin-stained tissue sections and immunohistochemistry, when available. RESULTS: Of the 13 cases, 1 aspirate was from a male breast and the rest were from female. Only 12 cases with documented histology were included in the study. Five of the 12 cases were diagnosed on FNAC as high grade lymphoma, 2 as low grade lymphoma, 2 as poorly differentiated malignant tumor/lymphoma, and 1 each as Hodgkin's lymphoma, acute myeloid leukemia (AML) deposit and immature lymphoid cells, ?leukemia/lymphoma deposit. The tumors manifested mostly as an unilateral mass (10 cases), with 2 cases presenting with bilateral breast lumps. The lymph nodes were involved in 8 cases. Histologically, 2 of the 12 cases were poorly differentiated malignant tumors. Of the remaining 10 cases, 8 were documented as non-Hodgkin's lymphoma and 1 each as Hodgkin's lymphoma, mixed cellularity and AML. CONCLUSION: FNAC is an inexpensive but highly useful diagnostic tool to distinguish between primary lymphoma and carcinoma of the breast. This helps with clinical management in avoiding unnecessary surgical procedures.     

Terminal deoxynucleotidyl transferase in diagnosis of lymphomas

TdT activities were determined on 29 specimens of mononuclear blood, bone marrow or lymph node cells from 18 patients with non Hodgkin's Lymphomas, 2 Hodgkin's patients and 3 patients with non neoplastic lymph nodes. The neoplastic cells were typed using tests detecting membrane markers (E, Em, SIg), and monoclonal antibodies (MoAb). In a group of 15 patients with Low Grade Malignant Lymphoma (L. lymphocytic, centrocytic and lymphoplasmocytic) 14 cases belonged to B cell phenotype lymphoma, with 3 cases among them with a moderate TdT activity. In one case of lymphocytic lymphoma the cells had the non T, non B, TdT+ characteristics. High TdT activity was observed in both examined patients with lymphoblastic lymphoma and in cells obtained from the lymph node of one Hodgkin's lymphoma case. Although our group was of heterogenic character, our investigations confirm the value of TdT as biochemical marker of immature lymphocytes and its usefulness for differential diagnosis of malignant lymphomas.