bromochloroacetic-acid and Hodgkin-Disease

We report 51 cases of a previously undescribed tumor of the distal extremities that is often mistaken for an inflammatory or infectious process, Hodgkin's disease, or various sarcomas. These lesions developed in patients of all ages (range, 4-81 yr; median, 40 yr) and affected the sexes nearly equally (27 men, 24 women). They presented as a painless mass of the fingers (14 cases), hand (11 cases), wrist or arm (10 cases), toe or foot (8 cases), or lower leg (5 cases), usually within the subcutaneous tissues. Grossly, they were infiltrative, multinodular masses characterized by a dense chronic inflammatory infiltrate that merged with a stroma, which varied from densely hyaline to focally myxoid and contained sheets of short spindled to rounded epithelioid cells. Focally, the epithelioid cells were extremely large with bizarre, vesicular nuclei and macronucleoli resembling Reed-Sternberg cells or virocytes. Despite the level of atypia, mitotic activity was low. The tumor cells consistently expressed vimentin but lacked a variety of other mesenchymal, epithelial markers, e.g., S100 protein, desmin, actin, neuron-specific endolase, epithelial membrane antigen, HMB-45, CD34) and leukocyte markers (CD15, CD30, CD45). Keratin was noted focally and weakly in four cases and CD68 focally in six cases, the latter suggesting that the cells had acquired phagocytic properties. Immunostains for cytomegalovirus were negative. Polymerase chain reaction for Epstein-Barr virus showed amplification levels consistent with latent infection in 4 of 10 cases, but no cases showed levels consistent with active infection. All of the bacterial and viral cultures were negative. Follow-up information was available in 27 cases. Recurrences developed in six patients (interval, 15 mo-10 yr), but there were no metastases or tumor-related deaths. In one patient, progressive proximal extension up the arm was noted. Although the most common submitting diagnosis was that of an inflammatory or infectious process, the negative studies for infectious agents, clinical behavior with local recurrences, immunophenotypic profile, and cytologic atypia support the idea that these are unusual mesenchymal neoplasms with at least the potential for local recurrence. It remains to be investigated whether with time these lesions will prove to have metastatic potential.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; Biomarkers, Tumor; Child; Child, Preschool; Diagnosis, Differential; DNA, Viral; Extremities; Female; Follow-Up Studies; Granuloma, Plasma Cell; Herpesvirus 4, Human; Hodgkin Disease; Humans; Keratins; Male; Middle Aged; Reed-Sternberg Cells; Sarcoma; Vimentin

Cytokeratin K19 (CK19) expression was evaluated by a reverse transcription PCR method (RT-PCR) in the RNA obtained from peripheral blood stem cell collections (PBSC) from four patients with breast cancers (BC) and 34 mononucleated blood cell (MBC) negative controls (17 PBMC from normal subjects 12 PBSC from different types of leukaemias--M3, M4Eo, M2, etc.--and two from patients with Hodgkin's lymphoma; and three bone marrow (BM) collections). Two BC tissues were taken as positive controls. The method studied (Datta YH, Paul T, Adams PT, Drobyski WR. Sensitive detection of occult breast cancer by reverse transcription polymerase chain reaction. J Oncol 1994;12:475-8) is sensitive enough to allow the detection of CK19 transcripts in a 10(-6) dilution of cDNA reverse transcribed from 1 microgram of BC RNA, but CK19 transcripts were also detected in 64% of the RNA obtained from the MBC controls. However, the amplified product detected in the control samples represents the transcript of the CK19 gene as confirmed by the results of Mae III digestion. It should be pointed out that although the CK19 expression was detected, the levels of expression in PBMC were almost negligible for they disappeared at 1:5 cDNA dilution. Moreover, a direct relationship between the number of BC cells added to PBMC and the increasing dilution levels of the cDNA necessary to prevent CK19 expression was observed. This allows us to conclude that the cDNA dilutions make it possible to distinguish the false from the true positive samples and that, in addition, the cDNA dilutions inform about the degree of BC cell contamination.

Topics: Breast Neoplasms; Case-Control Studies; DNA, Complementary; DNA, Neoplasm; Evaluation Studies as Topic; Female; Gene Expression; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Keratins; Leukemia; Leukocytes, Mononuclear; Polymerase Chain Reaction; Sensitivity and Specificity

We describe a case of synovial sarcoma occurring in a 36 year-old woman, 8 years after radiation therapy for Hodgkin's disease. The tumor showed histological, immunohistochemical, ultrastructural, and molecular features diagnostic of synovial sarcoma. To our knowledge, this is the first report of a fully documented case of radiation associated synovial sarcoma.

Topics: Adult; Biomarkers, Tumor; Female; Hodgkin Disease; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Mucin-1; Neoplasms, Radiation-Induced; Peripheral Nervous System Neoplasms; Sarcoma, Synovial; Translocation, Genetic

The sensitivity and specificity of a reverse transcription PCR method (RT-PCR) to detect cytokeratin K19 (CK19) expression was evaluated with the purpose of assessing its capability to detect the presence of breast cancer tumour cells in peripheral blood progenitor cell collection that had to be reinfused to breast cancer patients submitted to intensive chemotherapy as haematopoietic support.. Two breast cancers as positive samples were used and 34 samples of mononucleated blood cells as negative controls: 18 peripheral blood samples from normal subjects, 14 from different types of leukaemias (M3, M4Eo, M2, etc.) and two from two patients with Hodgkin's lymphoma. The method studied is a nested RT-PCR that amplifies the CK19 expression from the sample RNA extracted following the method of phenol-chloroform.. The right performance of the method is demonstrated by observing the detection of CK19 transcripts in the breast cancer RNA and by obtaining good blank results both with non transcribed RNA and with DNA. Moreover, the method has an excellent sensitivity such as to allow the detection of CK19 transcripts in a 10(-6) dilution of cDNA reverse transcribed from 1 microgram of breast cancer RNA. The CK19 transcripts were also detected in the 64% of RNA obtained from the mononucleated blood cells controls, although the percentage of positivities was lower (47%) in the RNA from peripheral blood samples. Nevertheless it should be remarked that the levels of CK19 expression in the blood mononucleated cells is almost negligible since it used to extinguish at 1:5 cDNA dilution.. The method studied is specific and has a high sensitivity that explains the detection of CK19 illegitimate expression approximately a half in mononucleated blood cells negative controls. However, the levels of CK19 expression in mononucleated blood cells were almost negligible and it used to extinguish at 1:5 cDNA dilution, therefore it could be concluded that the method might be useful to detect breast cancer occult tumours cells in mononucleated blood cell collection, always provided that a lower amount of cDNA is taken, thus decreasing to nil almost the false positive samples and keeping always a good sensitivity.

Topics: Biomarkers, Tumor; Breast Neoplasms; DNA, Complementary; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Hodgkin Disease; Humans; Keratins; Leukemia, Myeloid; Neoplasm Proteins; Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity

In this study coexpression of cytokeratin and desmin, and occasionally also Ki-1 antigen, was displayed in extrafollicular reticulum cells of reactive lymph nodes. The absence or expression of trace amounts of these proteins in normal lymphoid tissue suggests that activation of T cell regions is correlated with the increased frequency of cytokeratin, desmin and Ki-1 expressing cells, and therefore may be a transient phenomenon. S-100-positive interdigitating reticular cells were found occasionally in extrafollicular T cell region of normal lymph nodes. They were, however, more numerous in reactive lymphatic tissue. In the myasthenic thymuses cells forming Hassall's corpuscles displayed coexpression of cytokeratin, desmin and Ki-1 antigen. Medullary epithelial cells were also cytokeratin-positive and, additionally, Ki-1 antigen was expressed on some cells dispersed in whole thymic tissue. S-100-positive interdigitating reticular cells were especially numerous in the thymic medulla and some of them found inside the Hassall's corpuscles. In Hodgkin's disease deficiency of cytokeratin and desmin in extrafollicular reticulum cells is a constant phenomenon in spite of a classic inflammatory background. However, Ki-1 antigen displayed Reed-Sternberg cells which, similar as some thymic cell elements, appear to originate from stromal perivascular mesenchyme. This fact suggests that Reed-Sternberg cells in Hodgkin's disease are pathologic counterparts of extrafollicular reticulum cells which represent a cellular differentiation defect to produce desmin and cytokeratin but with a possibility of Ki-1 antigen expression. The consequence of this may be the disregulation of immune system and the observed immunologic abnormalities. Further studies are needed to elucidate the role of Epstein-Barr viruses in this process. S-100-positive interdigitating reticular cells were in close contact with Reed-Sternberg cells and they were especially large and with numerous cells processes in the mixed cellularity (MC) subtype. The occurrence of interdigitating reticulum cells with S-100 protein expression, especially numerous in the T cell region activated of peripheral lymphatic tissue, as well as their close contact with Reed-Sternberg cells and with cells forming Hassall's corpuscles suggest their eventual possible role in the function of the immune system.

Topics: Adolescent; Adult; Child; Desmin; Female; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Lymph Nodes; Lymphocyte Activation; Male; Middle Aged; Myasthenia Gravis; S100 Proteins; Thymus Gland

We describe two patients with nasopharyngeal carcinoma who initially presented with cervical lymphadenopathy. Lymph node biopsy specimens in each patient were initially diagnosed as Hodgkin's disease. In both cases, the neoplastic cells had large, vesicular nuclei with prominent eosinophilic nucleoli; some neoplastic cells were identified in lacunar spaces. In addition, numerous inflammatory cells were present, including eosinophils, lymphocytes, and plasma cells. At the time of referral, the correct diagnosis of metastatic carcinoma was made, and primary nasopharyngeal carcinomas were subsequently identified. The possibility of metastatic nasopharyngeal carcinoma should always be considered in adults with enlarged cervical lymph nodes that resemble Hodgkin's disease. The cytologic features of the malignant cells are the clue to the correct diagnosis. Immunophenotypic studies easily resolve this diagnostic dilemma if the possibility of metastatic nasopharyngeal carcinoma is considered.

Topics: Adult; Aged; Biopsy; Diagnosis, Differential; Eosinophils; Female; Hodgkin Disease; Humans; Immunophenotyping; Keratins; Lymph Nodes; Lymphatic Diseases; Lymphatic Metastasis; Lymphocytes; Male; Nasopharyngeal Neoplasms; Uterine Cervical Diseases

The authors report the histories of two patients with undifferentiated carcinoma metastatic to lymph nodes simulating the "syncytial variant" of nodular sclerosing Hodgkin's disease. One of the patients initially was treated for Hodgkin's disease, but the clinical evolution was more typical of carcinoma. Both lesions were characterized histologically by noncohesive aggregates of large neoplastic cells with abundant eosinophilic cytoplasm and conspicuous nucleoli. Although cells compatible with diagnostic Reed-Sternberg cells were identified in an "appropriate" cellular background in both patients, the diagnosis of carcinoma was supported by intense cytokeratin immunoreactivity. Subtle histologic clues that should suggest the possibility of metastatic carcinoma in a patient whose morphologic data suggests the syncytial variant of nodular sclerosing Hodgkin's disease include sinus infiltration, phagocytosis of neutrophils by tumor cells, marked nuclear anaplasia, and the presence of spindle-shaped tumor cells.

Topics: Adult; Antibodies, Monoclonal; Cell Nucleus; Diagnosis, Differential; Female; Genetic Variation; Hodgkin Disease; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Phagocytosis; Reed-Sternberg Cells; Sclerosis

Malignant angioendotheliomatosis (MAE) is a lethal intravascular proliferation which has been thought to be of endothelial origin. In order to characterize its cellular nature, we studied 15 cases of MAE immunocytochemically, using antisera for factor VIII-related antigen, cytokeratin, epithelial membrane antigen, vimentin, blood group isoantigens, thoracic duct lining cell antigens (TDLCA), common leukocyte antigen, and Ulex europaeus I lectin. In 14 of 15 cases, common leukocyte antigen was observed in malignant intravascular cells. Similar reactivity for factor VIII-related antigen was present in 14 cases, but was largely restricted to cells enmeshed in fibrin-platelet thrombi, and probably represents adsorption of platelet-derived factor VIII by tumor cells. All cases failed to bind Ulex europaeus lectin and lacked immunoreactivity for TDLCA, cytokeratin, epithelial membrane antigen, and blood group isoantigens; two manifested positivity for vimentin. Immunofluorescent microscopy of frozen tissue in one case showed monoclonal IgM-kappa immunoglobulin on the surfaces of tumor cells. Electron-microscopic study of three cases disclosed a predominant cell type lacking features of epithelial or endothelial differentiation; a minor cell population displayed endothelial characteristics and was thought to be reactive. Four patients with typical MAE also had extravascular large-cell lymphoma in lymph nodes, spleen, adrenal glands, stomach, or soft tissues. Six patients showed clinical evidence of autoimmune disease. These results suggest that MAE displays lymphoid rather than endothelial differentiation.

Topics: Aged; Angiomatosis; Antigens; Blood Group Antigens; Blood Vessels; Endothelium; Factor VIII; Female; Fluorescent Antibody Technique; Histocompatibility Antigens; Hodgkin Disease; Humans; Isoantigens; Keratins; Leukocyte Common Antigens; Lymphoid Tissue; Male; Membrane Proteins; Microscopy, Electron; Middle Aged; Mucin-1; Vimentin; von Willebrand Factor

The histologic and immunologic features of an unusual morphologic expression of nodular sclerosing Hodgkin's disease, which ahs been termed the "syncytial variant," are described. In biopsy material from 18 cases, numerous Reed-Sternberg cell variants were observed in sheets and cohesive clusters, and at least focal evidence of nodular sclerosis was present in each case. The granulocyte antibody anti-Leu M1 reacted with antigenic determinants in Reed-Sternberg cells and atypical variants thereof in 13 of the 18 cases; the lack of staining with antibodies reactive with the leukocyte common (T200) antigen (PD7/26), keratin (AE1), and S100 protein (polyclonal anti-S100) was helpful in excluding non-Hodgkin's lymphoma, carcinoma, and melanoma, respectively. This unusual form of nodular sclerosing Hodgkin's disease is important to recognize, since it may simulate metastatic neoplasms, thymoma, and non-Hodgkin's lymphoma.

Topics: Adolescent; Adult; Aged; Animals; Antibodies, Monoclonal; Diagnosis, Differential; Female; Histocompatibility Antigens; Hodgkin Disease; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Lymphoma; Male; Middle Aged; Neoplasm Metastasis; S100 Proteins

Immunocytochemical stains for three epithelial cell markers--keratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA)--have been examined on paraffin-embedded material from 14 patients with nasopharyngeal carcinoma (NPC). Tumour cells staining positively for keratin were found in all cases and for EMA in eight; two tumours contained CEA-positive cells. Seven cases of Hodgkin's disease and 24 non-Hodgkin's lymphomas were uniformly negative. Keratin is the most reliable epithelial marker for identifying NPC and excluding lymphoma. The regular finding of stainable keratin in non-keratinising and anaplastic NPC supports the view that NPC is a homogeneous group exhibiting variable degrees of squamous differentiation.

Topics: Antigens; Carcinoembryonic Antigen; Carcinoma; Cell Membrane; Diagnosis, Differential; Epithelium; Hodgkin Disease; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Nasopharyngeal Neoplasms