Syncytial Variant Research Articles

Respiratory Failure in a Patient with Hodgkin's Lymphoma Transforming into an Aggressive Syncytial Variant Infiltrating the Lung

INTRODUCTION: Pulmonary complications after hematopoietic stem cell transplant have a wide differential diagnosis. We report a patient with diffuse nodular disease three months after autologous bone marrow transplant.

Comparison of Fascin Expression in Anaplastic Large Cell Lymphoma and Hodgkin Disease

Diagnostic difficulties sometimes arise in distinguishing anaplastic large cell lymphoma (ALCL) from Hodgkin disease (HD), especially the syncytial variant. Study of the biologic features of diagnostic Reed-Sternberg cells in HD, in search of specific markers for Reed-Sternberg cells, has suggested fascin as a relatively specific and sensitive marker. We studied the frequency of fascin expression in 30 ALCLs and 34 cases of classic HD, including 17 cases of the syncytial variant. Staining with CD30 and anaplastic lymphoma kinase (ALK)-1 also was performed in all cases. All ALCL and HD cases showed membranous and Golgi zone CD30 positivity. Fascin stained all HD cases but also stained 67% (20/30) of the ALCLs in a cytoplasmic pattern. Fascin positivity was observed in 59% (10/17) of T-cell ALCLs and 77% (10/13) of null-cell ALCLs; ALK-1–positive ALCLs, regardless of origin, were usually fascin-positive (91% [10/11]). In conclusion, fascin shows strong positivity in all cases of classic HD but also is positive in the majority of ALCLs, including ALK-1–positive and ALK-1–negative cases. Positive staining for fascin is not useful for distinguishing ALCL from HD. In some cases, fascin negativity may help rule out classic HD.

Syncytial variant of nodular sclerosing hodgkin's disease diagnosed by sputum cytology - A case report

Mediastinal Hodgkin's disease in young females is usually of the nodular sclerosing type. Pulmonary involvement is seen in 15-50%cases of Hodgkin's disease. It is possible to suggest a diagnosis of Hodgkin's disease in sputum by the presence of Reed-Sternberg cells. We report herewith a case of a 22-year-old female diagnosed bypost-bronchoscopy sputum cytology and confirmed by histopathology. A transthoracic fine needle aspiration biopsy proved inconclusive.

Syncytial Variant of Nodular Sclerosis Hodgkinʼs Disease

*From the Department of Pathology and Laboratory Medicine and Division of Hematology-Oncology,† University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Reprint requests to: Kevin E. Salhany, MD, Department of Pathology and Laboratory Medicine University of Pennsylvania Medical Center 6 Founders Pavilion, 3400 Spruce Street Philadelphia, PA 19104. Supported in part by Grant #IRG-135L from the American Cancer Society (KES) and a McCabe Fund Award (KES).

Syncytial Variant of Nodular Sclerosis Hodgkinʼs Disease

Syncytial Variant of Nodular Sclerosis Hodgkinʼs Disease

Clonal VDJ Recombination of the Immunoglobulin Heavy Chain Gene by PCR in Classical Hodgkin’s Disease

Although Hodgkin's disease (HD) has been a subject of much investigation, fundamental questions remain unanswered regarding its lineage and clonality. The authors used a polymerase chain reaction (PCR) technique to investigate whether clonal Variable-Diversity-Joining recombination of the immunoglobulin heavy (IgH) chain gene, a phenomenon that characterizes clonal B-cell proliferations, exists in nodular sclerosing (NSHD) and mixed cellularity (MCHD) Hodgkin's disease (so-called "classical" Hodgkin's disease). The isolation of DNA from paraffin-embedded tissue sections allowed for direct correlation of PCR results with the cell populations that were analyzed. Thirty-two cases were studied. These included 12 cases in which the Reed-Sternberg (RS) cells expressed the B-cell antigen, CD20, and 10 cases that were classified as syncytial variant of NSHD (3 CD20+, 7 B-cell antigen negative). Overall, clonal patterns of VDJ PCR products were found in 14 of 32 (44%) cases. These clonal patterns were identified in 7 of 12 (58%) cases of CD20+ classical HD and in 7 of 20 (35%) cases of B-antigen-negative classical HD. Clonal patterns were found in 3 of 10 cases of syncytial variant of NSHD, including 2 of 3 (67%) CD20+ cases and 1 of 7 (14%) B-cell antigen-negative cases. The results of this study provide support that a subset of HD represents a clonal B-cell neoplasm, and indicate that clonal IgH VDJ sequences are more frequently found in CD20+ HD.

Primary Ki-1-positive anaplastic large-cell lymphoma: A distinct clinicopathologic entity

The morphology of anaplastic large-cell lymphoma (ALCL) is associated with a clinical syndrome of peripheral lymphadenopathy (> 80%) and frequent extranodal disease (> 40%) in children and young adults (median age < 40 yrs.). Skin lesions occur in more than 20% of patients; other extranodal sites are bone, soft tissue, gastro-intestinal tract, lung, and pleura. Marrow involvement is infrequent (< 10%). Features that distinguish ALCL from Hodgkin's disease (HD) are noncontiguous nodal disease (> 50%), infrequent mediastinal mass (< 20%), and frequent inguinal lymphadenopathy (> 40%). Most patients present with stage III/IV disease. Stage is highly predictive of achieving complete remission, disease-free survival, and overall survival. Localized skin lesions have an excellent prognosis and occasional spontaneous regressions are noted. Distinctive histopathologic features of ALCL are partial lymph node involvement with sinus infiltration, sparing of B-cell regions, and tumor cell pleomorphism. Other features are high mitotic rate, necrosis, fibrosis, and plasma cell infiltrates. Morphologic variants of ALCL resemble carcinoma, syncytial variant of nodular sclerosing HD, true histiocytic lymphoma or interdigitating cell sarcoma, and mycosis fungoides. ALCL can be distinguished from these morphologically similar disorders by immunophenotype (CD30+, CD45+, CD15-, EMA+, BNH9+, keratin-, lysozyme-). A recurrent cytogenetic translocation, t(2;5) (p23; q35), has been observed among morphologic variants, including a small-cell-predominant variant and tumor cell line which contains a spectrum of small cerebriform and large anaplastic CD30+ cells. 70% of ALCL cases are of T-cell lineage, 15% B, 5% T/B, and 10% undefined.(ABSTRACT TRUNCATED AT 250 WORDS)

National multicenter cohort histopathological retrospective study of hodgkin’s disease (HD)

Retrospective and histopathological study on 1096 cases of Hodgkin’s disease (HD) showed that the incidence of HD in lymph node biopsy was 3.87%, the ratio between HD and NHL in 1960s, 1970s and 1980s were quite similar. Among 1083 cases of HD with sex record, 787 were male, and 296 were female. The ratio of male to female was 2.65: 1, and the mean age was 31 years. According to Rye’s classification 274 were LP, 145 were NS, 511 were MC, 135 were LD and 19 were unclassified. The distribution of the four subtypes in this series showed that accounted LP for 25. 3% , NS for 13. 3%. MC for 47. 1% and LD for 12.4%. There were three major differences; 1. NS was much less, 2. LD was higher, and 3. NS-G2 was much more, when compared to the figures of other representative studies in western countries. In regard to the pathological diagnosis, residue follicles could be obtained in 42.8% of the HD lesions, and therefore, the presence of residue follicles would not exclude the positive diagnosis of HD. Typical R-S cells could be found only in 39.2% of these cases. The recently reported “syncytial variant” change was not a special feature of NS in our study. Primary extranodal HD was extremely rare in this study, and the mortality of HD in China seemed much higher than that in the advanced countries.

Metastatic Carcinoma in Lymph Nodes Simulating “Syncytial Variant” of Nodular Sclerosing Hodgkin's Disease

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.

Isolation of a type D retrovirus from B-cell lymphomas of a patient with AIDS

An atypical syncytial variant of a high-grade Burkitt's-type B-cell lymphoma from a patient with AIDS who was seropositive for human immunodeficiency virus type 1 was studied. A productive type D retrovirus infection was identified in early-passage cell lines derived from two lymphomas from this patient. Nucleotide and amino acid sequence analysis as well as immunologic reactivity indicated that the isolated virus was highly related to Mason-Pfizer monkey virus (MPMV). MPMV is an immunosuppressive type D retrovirus that causes an AIDS-like syndrome in rhesus macaques. Amplification of DNA from the patient's diagnostic bone marrow biopsy specimen by polymerase chain reaction generated the appropriate MPMV-specific fragments and indicated that the patient was infected with the MPMV-like retrovirus. In addition, the patient's serum contained antibodies which recognized type D viral env proteins (gp70 and gp20) and gag proteins (p27 and p14). Although there have been reports of human cell lines infected with type D retroviruses and of type D-reactive human sera, this is the first evidence of a type D retrovirus infection in a human confirmed by virus isolation, serum reactivity, and viral DNA identification in tumor tissue.

Altered pathogenesis in herpes simplex virus type 1 infection due to a syncytial mutation mapping to the carboxy terminus of glycoprotein B

A syncytial (syn) variant of herpes simplex virus type 1 strain 17 syn+ was selected by serial passage in heparin, a glycosaminoglycan which potently inhibits herpes simplex virus infectivity. This virus, 17 hep syn, is sixfold more heparin resistant than its parent. By using marker transfer techniques, its syn phenotype, but not heparin resistance, was mapped first to the BamHI G fragment (0.343 to 0.415 map units) and then to a 670-bp KpnI-PstI subclone (0.345 to 0.351 map units) encoding the carboxy terminus of glycoprotein B (gB). Three cloned syncytial recombinants were generated from cotransfections of 17 syn+ with either 17 hep syn BamHI-G or the 670-bp subclone. After footpad inoculation of mice, 17 hep syn was as virulent as its parent, despite reaching lower titers in feet, sciatic nerves, dorsal root ganglia, spinal cords, and brains. Animals infected with 17 hep syn or the gB recombinant viruses developed a unique pattern of disease that was strikingly different than that seen with wild-type virus: severe inflammation and edema of the inoculated limb and death without antecedent paralysis. Histopathologic examination revealed limitation of spinal involvement by 17 hep syn to the dorsal aspect of the cord and decreased virus-induced damage in the central nervous system. The genetically unrelated syn variant MP, in contrast, was avirulent and did not cause severe local inflammation. After intracerebral inoculation, 17 hep syn was highly virulent and replicated to high titers in the brain. Yet, unlike the parental virus, it resulted in an altered distribution of herpes simplex virus antigens, which were limited to the ependymal and subependymal regions surrounding the lateral ventricles. Despite their syncytial phenotype and pathogenic properties, the recombinant viruses, unlike 17 hep syn, were not heparin resistant. We conclude that a transferable alteration in the 670-bp carboxy-terminal portion of the glycoprotein gB gene of 17 hep syn results in both its syncytial phenotype and the unique pattern of disease that it causes but does not result in heparin resistance. These observations provide direct biological evidence for an important role for herpes simplex virus gB in pathogenic events both at the peripheral site of infection and within the nervous system.

Fine-needle aspiration evaluation of lymphoproliferative lesions in human immunodeficiency virus-positive patients. A multiparameter approach

Forty-six fine-needle aspirates of lymphoproliferative lesions from 31 human immunodeficiency virus (HIV)-positive patients were reviewed using cytomorphologic, immunocytochemical, flow cytometric (FCM), cytogenetic, and molecular studies. There were 29 lymphomas (15 small non-cleaved cell [SNCL], 11 large cell [LCL], one small lymphocytic, and two Hodgkin's), 14 reactive hyperplasias, and three "atypical lymphoid proliferations." The reactive hyperplasias were characteristically polymorphic and polyclonal lymphoid populations; six of seven were diploid on FCM, the seventh was hypodiploid. Higher proliferative indices (mean, 11.6%) and higher RNA indices (mean, 1.2) characterized this subgroup compared with published reactive lymphoid hyperplasias from patients without HIV positivity. Aspirates of SNCL showed monotonous populations of intermediate-sized cells except in one patient where a giant cell syncytial variant occurred. Nine of 13 SNCL aspirates showed light chain restriction. JH rearrangement revealed B-cell lineage in one aspirate in which immunocytochemical study was negative for Kappa, lambda, B1, and Leu-4. Nine of 12 SNCL were diploid; the mean proliferative index was 25.6% and the mean RNA index 2.3. Chromosomal translocations involving the c-myc locus were demonstrated in five of seven SNCL aspirates karyotyped. Five of eight LCL showed light chain restriction the remaining three showed null cell phenotype. Large cell lymphomas were diploid on tetraploid with the mean proliferative index of 22.0% and mean RNA index of 2.2. One of two LCL aspirates karyotyped demonstrated c-myc translocation. Despite the multiparameter approach, a definitive diagnosis could not be reached in three aspirates.

Syncytial Variant of Nodular Sclerosing Hodgkin's Disease Expressing T-cell Antigens

Syncytial Variant of Nodular Sclerosing Hodgkin's Disease Expressing T-cell Antigens

Syncytial variant of nodular sclerosing Hodgkin's disease. A new clinicopathologic entity

The clinicopathologic and histopathologic features of an unusual morphologic variant of nodular sclerosing Hodgkin's Disease (HD) termed the syncytial variant has been reported recently. We report eight new cases with this unique morphology, identified by reviewing the histopathology of 58 patients with nodular sclerosing HD treated in our institute between 1982 and 1988. The clinicopathologic and histopathologic data of these cases are reported and we emphasize this new entity and the difficulties encountered in the morphologic diagnosis. All of the eight patients had a difficult initial clinical course, and were in a clinically advanced stage of the disease at the time of diagnosis. We cite a statistical comparison of the clinical features of the different forms of nodular sclerosing HD.

Utility of combining antigranulocyte with antileukocyte antibodies in differentiating Hodgkin's disease from non-Hodgkin's lymphoma.

The authors have reviewed their experience using the antigranulocyte marker, anti-Leu-M1, in combination with the antileukocyte marker, PD7/26, applied to paraffin sections of malignant lymphomas difficult to subclassify using morphologic criteria. The study group consisted of 73 lymphomas; 53 cases of Hodgkin's disease and 20 cases of non-Hodgkin's lymphoma. Leu-M1 was expressed by the Reed-Sternberg and Hodgkin's cells in 33 (62%) of the cases of Hodgkin's disease. The Reed-Sternberg and lymphocytic and histiocytic (L&H) cells in four cases of lymphocyte-predominant Hodgkin's disease were Leu-M1 negative. The Reed-Sternberg cells and L&H cells expressed leukocyte common antigen, utilizing the monoclonal antibody PD7/26, in seven (13%) of the 53 cases including the four cases of lymphocyte-predominant subtype (three nodular, one diffuse). The Reed-Sternberg-like cells in four (20%) of the cases of non-Hodgkin's lymphoma were stained by anti-Leu-M1 whereas, in 12 cases (60%) these cells were stained by PD7/26. The combination of anti-Leu-M1 and PD7/26 provided more useful information than that provided by anti-Leu-M1 alone by providing immunologic support for the diagnosis of lymphocyte-predominant Hodgkin's disease and by identifying cases which stained with neither antibody. The authors interpret the immunologic findings in the latter cases as equivocal. These studies were most helpful in cases with many atypical cells and provided unequivocal support for the diagnosis of Hodgkin's disease in six of 11 cases of the "syncytial variant," a form of the nodular sclerosing type characterized by cohesive aggregates of Reed-Sternberg cells and lacunar variants, not uncommonly misdiagnosed using only morphologic criteria.

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-.

The “Syncytial Variant” of Nodular Sclerosing Hodgkinʼs Disease

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.

Characterization of virus obtained from MDBK cells persistently infected with a variant of herpes simplex virus type 1 strain MP [HSV-1(MP)

Virus clones which express glycoprotein gC (gC +) were obtained from two persistently infected (p.i.) MDBK cell lines which had been independently established by infection with HSV-1(MP)10311, a gC − syncytial (syn) variant of herpes simplex virus type 1 strain MP [HSV-1(MP)]. The gC + revertants were syn in MDBK, HEp-2, and Vero cell lines and in primary human fibroblasts; this offers further evidence that glycoprotein gC does not inhibit cell fusion. The gC + revertants represented from 70 to 100 percent of the virions present in the virus populations examined, thus suggesting a possible selective advantage of the gC + revertants in this system of persistent infection.

Influence of genetic and physiological properties of the host cell on the cytopathic expression of herpes simplex virus

Two plaque morphology variants, a cell aggregating variant and a syncytial variant, were isolated from MDBK cells infected with the MP mutant of herpes simplex virus, type 1. The variants differed in the polypeptides produced in infected MDBK cells. The properties of the variants were stable on passage in cells and both variants produced only syncytia in KB and Hep-2 cells. The physiological state of MDBK cells influenced the cytopathological expression of the infecting virus, so that, under certain conditions, each variant could shift from one type of plaque morphology to the other. However, attempts to correlate this plaque morphology shift with a difference in the glycopolypeptides synthesized in the infected cells were unsuccessful.