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Biomedical subjects

L M Weiss

Publications and source records attributed to L M Weiss.

At least 109 records · Page 6Linked to original sources

Molecular diagnosis of gastrointestinal infections associated with HIV infection.

Developments in medical microbiology in the past 20 years have had a profound impact on our understanding of infectious diseases and have led the way in the development of new diagnostic techniques. Molecular diagnostic techniques are generally more sensitive, specific, and rapid than conventional methods by which infectious agents are detected. For many of the opportunistic infectious agents of the gastrointestinal tract found in HIV-infected individuals, the application of molecular diagnostic techniques to the clinical laboratory is in its infancy. In this article, methods by which these techniques can be evaluated are demonstrated, and the current status and potential future application of these techniques for each gastrointestinal opportunistic pathogen are described.

AIDS-Related Opportunistic Infections↗

Hodgkin's disease of the esophagus.

A 61-year-old man with acquired immunodeficiency syndrome (AIDS) sought care because of the onset of progressive dysphagia. He was found to have a perforated, fungating esophageal mass. The combined histologic and immunologic findings were diagnostic of Hodgkin's disease, nodular sclerosis type, lymphocyte-depleted variant, arising in the esophagus. The Reed-Sternberg cells and mononuclear variants were positive for Epstein-Barr virus (EBV) latent membrane protein (LMP1) and EBV RNA. Occasional small lymphoid cells were also positive for EBV RNA. Polymerase chain reaction studies demonstrated the presence of EBV type A without deletion of the EBV LMP1 gene. Other authors have reported an increased frequency of type B EBV and deletion of the EBV LMP1 gene in cases of human immunodeficiency virus-associated Hodgkin's disease. Hodgkin's disease arising in the esophagus is rare in immunocompetent patients. However, in the presence of AIDS, Hodgkin's disease should be considered in the differential diagnosis of patients with signs or symptoms of esophageal disease.

Acquired Immunodeficiency Syndrome↗

Detection of Epstein-Barr virus in the L & H cells of nodular lymphocyte predominance Hodgkin's disease: report of a case documented by immunohistochemical, in situ hybridization, and polymerase chain reaction methods.

Although Epstein-Barr virus (EBV) is commonly present in the neoplastic Reed-Sternberg and Hodgkin cells of the mixed cellularity, nodular sclerosis, and lymphocyte depletion types of Hodgkin's disease (HD), EBV is rare in the neoplastic cells of the nodular lymphocyte predominance type of HD, particularly in the United States. We describe a 19-year-old Hispanic man in whom nodular lymphocyte predominance HD involved a cervical lymph node. Epstein-Barr virus was identified in the neoplastic L & H cells by using in situ hybridization for EBV RNA and immunohistochemical staining for EBV latent membrane protein-1. Polymerase chain reaction studies demonstrated the type A strain of EBV. The presence of EBV in this case may be related to drainage of the virus from the oropharynx to the cervical lymph node. The presence of EBV also may be related to this patient's Hispanic ethnic origin.

Adult↗

Splenic mesothelial cysts mimicking lymphagiomas.

Lymphangiomas of the spleen may occur as part of lymphangiomatosis or may represent solitary lesions. Solitary splenic lymphangiomas are described traditionally as subcapsular, multicystic proliferations that are often incidental findings. Six cases of splenic tumors with morphologic features similar to those described for solitary lymphangioma were studied using an immunohistochemical panel that included epithelial and vascular markers. None of the patients had evidence of lymphangiomatosis, and all tumors were incidental findings in splenectomy specimens. All cases demonstrated lining cells that were positive for keratin and the mesothelial cell-associated antibody HBME-1 but were negative for the vascular markers Factor VIII-related antigens, CD31, and CD34. The immunohistochemical findings are suggestive of a mesothelial derivation of these multicystic proliferations rather than representing true lymphangiomas.

Adult↗

Transformation of follicular lymphoma into CD30-large cell lymphoma with anaplastic cytologic features.

The natural history of follicular lymphoma is to accrue large cells and become diffuse, resulting in progression/transformation to a higher-grade lymphoma. Histologic transformation occurs in approximately 60% of patients. Most often, follicular lymphomas transform into diffuse large cell lymphoma, but transformation to lymphomas classified using the Working Formulation as diffuse mixed, large cell immunoblastic, or small noncleaved cell also have been reported. Evidence of transformation may be found over time in sequential biopsy specimens, or may coexist in the same biopsy specimen. Here, we describe six cases of follicular lymphoma, large cell in five cases and mixed in one case, that transformed into a diffuse or sinusoidal CD30 antigen-positive large cell lymphoma with anaplastic cytologic features. Both the follicular and diffuse/sinusoidal components were of B-cell lineage, positive for the CD20 antigen and negative for the CD3 and CD43 antigens. The neoplastic cells expressed monotypic immunoglobulin light chain in five cases, three kappa and two lambda. BCL-2 protein was positive in four tumors, in both the follicular and diffuse/sinusoidal components in three cases, and only in the latter component in one case. Using the polymerase chain reaction (PCR), three of six cases had monoclonal immunoglobulin heavy chain gene rearrangements. The t(14;18) was not amplified in any case. Using reverse transcriptase (RT)-PCR, the t(2;5) was amplified in one of four tumors. This report highlights the heterogeneity of B-lineage anaplastic large cell lymphomas and indicates the need to consider antecedent follicular lymphoma in any B-cell lymphoma with anaplastic cytologic features.

Adult↗

Splenic vascular tumors: a histologic, immunophenotypic, and virologic study.

Vascular tumors of the spleen include several different entities, some of which are unique to that organ. Twenty-two such proliferations were studied, including 10 hemangiomas, six littoral cell angiomas, four angiosarcomas, and two hamartomas. The hemangiomas included seven with localized tumors and three with diffuse angiomatosis of the spleen. All cases were studied by paraffin section immunohistochemistry with a large panel of antibodies. In addition, all cases were studied for the presence of the Kaposi's sarcoma-associated herpesvirus (KSHV) using the polymerase chain reaction. The morphologic findings were similar to those previously reported. All proliferations were vimentin positive, and one angiosarcoma was focally keratin positive. All cases reacted for CD31, whereas 20 of 22 were positive for von Willebrand's factor and 19 of 22 were positive for Ulex europeaus. CD34 expression in lining cells was identified in 10 of 10 hemangiomas, two of four angiosarcomas, and one of two hamartomas, whereas all six cases of littoral cell angioma were negative. CD68 was expressed in all cases of littoral cell angioma but was also positive in all three diffuse hemangiomas, two of seven localized hemangiomas, and two of four angiosarcomas. CD21 expression was restricted to the lining cells of littoral cell angioma, and CD8 expression was only identified in two of two hamartomas and two of four angiosarcomas. KSHV was not detected in any of the cases. These findings suggest that there are distinct immunophenotypic as well as morphologic features of splenic vascular tumors. Littoral cell angiomas have a characteristic CD34-/CD68+/CD21+/CD8- immunophenotype and hamartomas have a characteristic CD68-/CD21-/CD8+ phenotype. The frequent CD68 expression in diffuse hemangioma suggests an immunophenotypic difference from localized hemangioma of the spleen.

Actins↗

Intravascularly disseminated angiosarcoma: true neoplastic angioendotheliomatosis? Report of two cases.

Although vascular invasion is common in many malignant tumors, disseminated intravascular anaplastic neoplasms with occult primary tumor are rare occurrences. Intravascular malignant lymphoma, also called angiotropic lymphoma, is a rare variant of large cell lymphoma predominantly involving vessels in multiple organs, and usually without significant nodal involvement. Although initially misinterpreted as an endothelial neoplasm-angioendotheliomatosis-immunohistochemical studies subsequently proved it to represent a peculiar form of malignant lymphoma. In this report, we describe two patients with extensive intravascular dissemination of angiosarcoma initially without clinically obvious primary tumor. These may be interpreted as examples of true angioendotheliomatosis. In each case the immunohistochemical studies ruled out the most common intravascular malignant neoplasms. The diagnosis of intravascular angiosarcoma was confirmed by the immunoreactivity of the tumor cells to several markers of endothelial lineage in both cases. Thus, angiosarcoma may present with intravascular dissemination and occult primary tumor and closely resemble metastatic carcinoma, melanoma, or angiotropic lymphoma. Immunohistochemical studies are crucial in ruling out these possibilities and in confirming the endothelial origin of the neoplastic cells.

Adult↗

Neurofibroma and cellular neurofibroma with atypia: a report of 14 tumors.

The clinical significance of nuclear atypia in neurofibromas that lack necrosis or significant mitotic activity has not been systematically studied. We reviewed 14 neurofibromas from six patients with mild to marked nuclear atypia, with low mitotic activity in some tumors. Five tumors also had areas of increased cellularity consistent with cellular neurofibroma. Necrosis was absent. All patients were treated by conservative excision. Clinical follow-up, ranging from 8 months to 6 years, showed that none of the tumors recurred or metastasized. To further characterize these neoplasms, we assessed p53 expression, proliferation rate, and DNA content because these methods have been suggested by others as useful in differentiating benign from malignant nerve sheath tumors. p53 expression was detected by immunostaining in one tumor with 5% positive cells and in two tumors with rare positive cells (<1%). The remaining 11 tumors were negative. Tumor cell proliferation rate as determined by Ki-67 immunostaining showed <5% positive cells in 13 tumors. In one tumor, 10% of the cells were Ki-67 positive. Using flow cytometry methods and paraffin-embedded tissue, all tumors had diploid DNA content with an S phase fraction ranging from 5.2% to 18.2% (mean 9.4%). No significant differences were observed between the neurofibromas and cellular neurofibromas. For comparison, we studied three malignant peripheral nerve sheath tumors (MPNSTs). All MPNSTs had relatively high p53 (range 10-16%; mean 12%) and Ki-67 (range 32-42%; mean 38.0%) staining. One of the MPNSTs was aneuploid. The S phase fraction of the MPNSTs ranged from 8.1% to 51.8% (mean 28.6%). These results suggest that clinically benign neurofibromas, both usual and cellular types, can have significant cytologic atypia that can be accompanied by low mitotic activity. Conservative surgical excision for these tumors is adequate. The results of p53 and Ki-67 immunostaining and DNA content and S-phase analysis by flow cytometry support this interpretation. In addition, in tumors with borderline histologic findings, results of these ancillary studies may be useful in distinguishing benign from malignant nerve sheath tumors.

Adult↗

Nasopharyngeal carcinoma, with emphasis on its relationship to Epstein-Barr virus.

Nasopharyngeal carcinoma (NPC) is an epithelial tumor with a distinct geographic distribution and characteristic histologic appearance. It is rare in Europe and North America, but it is among the most common cancers in southern China. Genetic predisposition, environmental factors, and Epstein-Barr virus (EBV) all have been associated with the pathogenesis of this tumor. There is an increasing body of evidence that among all these factors, EBV appears to be the strongest and most consistently related factor. According to the current sensitive in situ hybridization methods for the detection of EBV-encoded small RNAs (EBER), almost 100% of cases of NPC, irrespective of their histologic subtypes, have demonstrable EBERs in the nuclei of the tumor cells. In this review paper, we discuss the predisposing genetic and environmental factors and the role of EBV in the pathogenesis of this tumor with particular emphasis on the role of EBV.

Adolescent↗

Clinicopathological consultation. Lymphoepithelial carcinoma of the larynx hypopharynx, and trachea.

Lymphoepithelial carcinoma of the larynx, hypopharynx, and trachea is a rare neoplasm composed of large, poorly differentiated, nonkeratinized cells intermingled with small nonneoplastic lymphocytes and plasma cells. It is histologically similar to its more common counterpart occurring in the nasopharynx. In contrast to nasopharyngeal carcinoma, most cases have not been associated with Epstein-Barr virus (EBV), although rare cases have been reported to be EBV-positive. The diagnosis often requires immunohistochemistry or electron microscopy for confirmation. The neoplasm seems to behave in a fashion reminiscent of nasopharyngeal carcinoma. Lymph node metastasis occurs in the majority of patients, and eventual visceral dissemination occurs in one fourth. Radiotherapy is the main treatment for the primary tumor and regional metastases, but chemotherapy is indicated for more advanced disease. The initial stage is the primary determinant of prognosis. Death from disease occurs in about one third of patients.

Carcinoma, Squamous Cell↗

Non-Hodgkin's lymphoproliferative disorders involving the spleen.

One hundred eight splenectomy specimens involved by lymphoid neoplasms were studied to assess the frequency and pattern of involvement of the various disease groups. Cases were classified by the Working Formulation as well as by the Revised European-American classification of lymphoid neoplasms. Including the more recently described disease entities, large cell/immunoblastic lymphomas were the most common neoplasm, both primarily and secondarily, to involve the spleen (33.3% of all cases). The next most common lymphoid neoplasm to involve the spleen was chronic lymphocytic leukemia/ small lymphocytic lymphoma, found in 19.4% of cases, followed by follicular center cell lymphoma (13.0%), lymphoplasmacytoid lymphoma (9.3%), splenic marginal zone lymphoma (8.3%), mantle cell lymphoma (6.5%), and hairy cell leukemia (6.5%). The remaining 3.7% of cases included T-cell proliferations and one difficult-to-classify mixed cell lymphoma. More than 95% of the cases could be placed into one of three morphologic patterns of splenic involvement, i.e., 57.4% of spleens were involved by predominantly white pulp disease, 20.4% by predominantly nodular disease, without a predilection for white or red pulp, and 17.6% by predominantly red pulp disease. Although the white pulp and nodular patterns were primarily, but not exclusively, B-cell disorders, specimens with predominantly red pulp disease included all of the cases of hairy cell leukemia, as well as cases of both B- and T-cell lymphomas.

Adult↗

Immunophenotype of Reed-Sternberg and Hodgkin's cells in sequential biopsy specimens of Hodgkin's disease: a paraffin-section immunohistochemical study using the heat-induced epitope retrieval method.

Other studies have shown that the immunophenotype of Reed-Sternberg and Hodgkin's (RS-H) cells in Hodgkin's disease commonly changes over time, as shown by examination of multiple biopsy specimens obtained from an individual patient. In this study we analyzed 96 sequential biopsy specimens (>1 month apart) obtained from 44 patients (nodular sclerosis, 34 specimens; mixed cellularity, 5; lymphocyte depletion, 1; unclassified, 4) using fixed, paraffin-embedded sections; heat-induced epitope retrieval (HIER); a panel of antibodies specific for the CD3, CD15, CD20, CD30, CD43, CD45/45RB, and CD79a antigens and Epstein-Barr virus latent-membrane protein; and a streptavidin-biotin method. In selected cases in which immunophenotypic changes occurred, studies were repeated using enzyme predigestion instead of HIER. There was no change in the immunophenotype of the RS-H cells in 36 (82%) of 44 patients. In 8 patients (18%), the immunophenotype of the RS-H cells varied in expression of one or two antigens. The antigens that varied were as follows: CD30, 3 patients; CD15, 3 patients; CD20, 1 patient; and CD15 and CD30, 1 patient. We conclude that the immunophenotype of RS-H cells in Hodgkin's disease is relatively stable over time and that CD15 and CD30 are the most common antigens that change. The frequency of immunophenotypic changes, 18%, is substantially lower than that reported previously. One likely explanation for this discrepancy is that we used HIER, a relatively recent innovation in diagnostic immunohistochemistry that has been shown to reduce artifacts attributable to inconsistent fixation and processing. The significance of immunophenotypic variation in eight cases (18%) is uncertain. This phenomenon may represent true biologic changes in RS-H cells. Alternatively, these changes may be attributable to artifacts secondary to inconsistent fixation or processing that HIER cannot overcome.

Adolescent↗

Donor origin of posttransplant lymphoproliferative disorder localized to a liver allograft: demonstration by fluorescence in situ hybridization.

SETTING: Posttransplant lymphoproliferative disorders in solid organ transplantation are mostly of recipient origin. We report an unusual case of posttransplant lymphoproliferative disorder following liver transplantation with localized limited involvement of the solid organ allograft. DESIGN: Tissues were obtained at the time of surgery and evaluated by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization with chromosome X and Y centromeric probes. PATIENT: A 53-year-old Hispanic man with hepatic failure due to hepatitis C virus who underwent orthotopic liver transplant from a female donor and developed posttransplant lymphoma in the transplanted liver. INTERVENTION: Withdrawal of immunosuppression, resection of liver allograft, and second transplant. RESULTS: This posttransplant lymphoproliferative disorder was clearly shown to be derived from Epstein-Barr virus-infected donor lymphoid cells. This was demonstrated by fluorescence in situ hybridization for X and Y chromosomes in paraffin sections in a sex-mismatched transplant. Despite aggressive histology (monoclonal B-cell immunoblastic lymphoma) and lack of response to withdrawal of immunosuppression, the posttransplant lymphoproliferative disorder was successfully managed by repeat liver transplantation without recurrence. CONCLUSION: Fluorescence in situ hybridization was used to prove donor derivation in a posttransplant lymphoma of the liver. Allograft-localized donor posttransplant lymphoproliferative disorder may represent a unique category with more favorable prognosis requiring different clinical management from other cases.

Female↗

Myocardial G proteins in murine Chagas' disease.

G protein alpha subunits and their corresponding mRNA levels were determined in hearts obtained from mice infected with Trypanosoma cruzi, the etiologic agent of Chagas' disease. Protein and mRNA levels of the inhibitory G proteins G alpha i2 and G alpha i3 were increased at 21 and 30 days postinfection (PI). After 60 days, the abundance of protein and corresponding mRNA for G alpha i2 and G alpha i3 were no longer significantly different from uninfected mice. Twenty-one days after infection, G alpha s protein levels decreased markedly, but mRNA for the stimulatory protein did not change. Similar to the Gi proteins, by 60 days differences in G alpha s protein between infected and uninfected mice were no longer evident. There was an increase in the magnitude of G beta subunit protein 21 and 30 days PI as compared with uninfected mice. However, 60 days PI the G beta subunit protein decreased to control levels. The close relationship between the infection-associated increase in G alpha i protein and mRNA suggests that control of protein expression is likely to be exerted at the transcription level. In contrast, control of infection-associated decrease in Gs appears to be at the translational level.

Animals↗

The effect of decalcification on in situ hybridization.

In situ hybridization (ISH) for mRNA polyadenylated sequences was performed on 25 non-neoplastic and neoplastic decalcified, paraffin-embedded tissues using a poly d(T) oligonucleotide probe to assess the efficacy of this molecular diagnostic tool on decalcified tissue samples. Three commercially available decalcifying agents were used, including one EDTA-based solution (Versenate) and two hydrochloric acid-based solutions (S/P Decal, RBD). Before decalcification, the tissues were fixed in formalin for 6, 24, and 72 hours, respectively. The results of ISH performed on decalcified tissues were compared with the results from the nondecalcified control samples for each tissue using a numeric scoring system (0, negative; 4, strong positivity equal to control; 5, stronger than control). There was generally excellent reactivity when using Versenate (mean, 4.15), good reactivity with S/P Decal (mean, 3.17), and fair-to-poor reactivity with RBD (mean, 1.69) (all P values < .0001). The length of time in formalin did not affect the outcome of ISH on these tissues. We conclude that ISH can be performed with success on decalcified, paraffin-embedded tissues when using Versenate, an EDTA-based agent. Although accurate results might be obtained with S/P Decal and RBD, caution should be exercised when using these two hydrochloric acid-based solutions because they might produce false-negative results.

Chelating Agents↗

Clonality in lymphocyte predominance Hodgkin's disease.

Abundant evidence has led to the clinical and biological separation of lymphocyte predominance from other types of Hodgkin's disease. However, it is still not clear whether lymphocyte predominance represents a polyclonal reactive lesion (possibly representing an abnormal immune disorder), a polyclonal or oligoclonal preneoplastic disorder or a monoclonal neoplastic disorder. The clinical and histological features are distinctive, but they do not provide clear indications of the nature of lymphocyte predominance. Some immunohistochemical and in situ hybridization studies have shown monotypic light chain restriction in the L&H cells, almost always of kappa type, implying a monoclonal process. Southern blotting studies are of limited utility, given their relatively low sensitivity and the rarity of L&H cells within involved tissues. Polymerase chain reaction studies have yielded conflicting results. Some, but not all, have demonstrated monoclonal populations in tissue extracts. Single cell PCR studies have generally not found monoclonal populations, although one case stands as an exception. Cases of large cell lymphoma complicating lymphocyte predominance have been monoclonal by polymerase chain reaction and clonospecific primers derived from these clones have demonstrated similar populations in the corresponding lymphocyte predominance tissues in some, but not all, studies.

Blotting, Southern↗