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Posttransplant lymphoproliferative disorder (PTLD) is an infrequent complication of transplantation in children, and this report emphasizes the value of tonsil and adenoid biopsy in the early management of this potentially life threatening condition. In all three cases biopsy specimens of tonsils and adenoids were diagnostic of polymorphic diffuse B-cell hyperplasia (PBCH). Immunophenotyping showed no immunoglobulin (Ig) light chain restriction, although immunoglobulin heavy chain (IgH) gene rearrangement was monoclonal in two cases. Despite an absence of serological evidence for acute Epstein-Barr virus (EBV) infection, EBV was detected in all cases by semiquantitative polymerase chain reaction (PCR) for EBV DNA, by in situ hybridization for EBV mRNA (EBER), and by immunoperoxidase for EBV latent membrane protein (LMP). All three patients were treated with reduced immunosuppression and acyclovir and are well (19, 28, and 28 months' follow-up) with no recurrence. Children without previous EBV exposure may develop PTLD localized to the tonsils/adenoids, and biopsy specimens of these tissues may permit early diagnosis and clinical intervention. Despite monoclonal gene rearrangement in two cases, overall features were not indicative of malignancy. Strong association with EBV is helpful in confirming the diagnosis of PTLD and is consistent with initial presentation in the tonsils/adenoids.

p53 Protein is a 53-kd nuclear phosphoprotein believed to play an important role in controlling proliferation of neoplastic and normal cells. This "natural tumor suppressor" can be rendered ineffective (or oncogenic) by mutations in the p53 gene or by interactions with proteins synthesized by DNA-transforming viruses, including specific subtypes of human papillomavirus (HPV). We describe the localization of p53 protein in association with HPV in paraffin sections of a spectrum of benign, dysplastic, and malignant anogenital squamous epithelia using immunohistochemical and in situ hybridization techniques. p53 Was detected in 81% of the 48 cases studied. Immunoreactivity for p53 was seen in 83% of the benign and low-grade squamous intraepithelial lesions (SILs), in 73% of the high-grade SILs, and in 86% of the infiltrating squamous carcinomas. In high-grade SILs p53 staining was frequently observed in individual nuclei at various levels of the abnormal epithelium and in the basal layer of the adjacent epithelium, while in squamous metaplasia and low-grade SILs immunostaining for p53 was limited to the basal layer of the epithelium. p53 Was detected in a slightly higher percentage of HPV-positive than HPV-negative epithelia as determined by in situ hybridization. No correlation was observed between p53 immunoreactivity and HPV subtypes. p53 Protein and HPV were detected in anal lesions from a small group of human immunodeficiency virus-positive individuals. Antibodies currently available mainly demonstrate mutant forms of p53 protein that are associated with longer half-lives than the wild-type protein, but demonstration of p53 protein overexpression is not necessarily indicative of malignancy.

The histogenesis of adenomatoid tumors has been a source of controversy. Although most investigators favor a mesothelial derivation, recent ultrastructural evidence suggests that some adenomatoid tumors may be vascular neoplasms. This study reports the pattern of staining of seven adenomatoid tumors with antisera to keratin, factor VIII, and carcinoembryonic antigen (CEA), using an immunoperoxidase technique. All the tumors revealed strong cytoplasmic staining for keratin with no staining for factor VIII (an endothelial cell marker) or CEA. An identical staining pattern was evident in normal and reactive mesothelial cells. These findings support a mesothelial rather than an endothelial derivation for the tumors studied.

The clinical, pathologic, and immunologic features in nine cases of non-Hodgkin's lymphoma of the multilobated B-cell type are described. Clinical and phenotypic heterogeneity was observed in these B-cell neoplasms. A probable follicular center cell derivation for these cytologically unusual B-cell lymphomas is supported by antecedent histories of follicular center cell neoplasms in three cases; a focal nodular pattern in one case; the demonstration of peanut lectin (PNA) receptors, a marker for follicular center cells, on neoplastic multilobated B cells; and immunoultrastructural studies of nonneoplastic tonsillar cells that identified and characterized rare multilobated cells, immunoreactive for B1, B2, and Ia membrane antigens, a phenotype consistent with follicular center-type cells. Comparison of B- and T-cell multilobated lymphomas revealed that only immunologic studies accurately discriminated between these neoplasms.

Lymph nodes from homosexual men with persistent generalized adenopathy were evaluated for distribution of T-cell phenotypic subsets and surface immunoglobulin(SIg)-bearing lymphocytes. Electron microscopy revealed tubulovesicular structures within lymphocytes but no multivesicular rosettes. Eight to 33 per cent of the lymphocytes within germinal centers were suppressor T cells, compared with germinal centers from control lymph nodes, in which these cells were rare (P = 0.002). Significantly greater percentage of suppressor/cytotoxic T lymphocytes were also present in the paracortex and follicular mantles of lymph nodes from the homosexual group (P = 0.002 and 0.007, respectively). Percentages of helper T lymphocytes were significantly decreased in germinal centers (P = 0.008) and paracortical regions (P = 0.002). Florid follicular hyperplasia with aberrations in follicular architecture was the most common histologic pattern, but one node with diffuse hyperplasia and subtotal effacement of architecture revealed depletion of SIg-bearing lymphocytes and increased numbers of suppressor T cells. Reversed helper-to-suppressor T-cell ratios in lymph nodes from homosexuals with generalized adenopathy may be related to viral infection and contribute to immune deficiency in this group.

Use of monoclonal antibodies directed against T cell antigens for the phenotypic characterization of neoplastic lymphoid cells in peripheral T cell lymphomas is described. Studies of cryostat sections revealed the distribution of T cell subsets in nodal and extranodal infiltrates, and immuno-ultrastructural techniques demonstrated discrete localization of T cell antigens to the cytoplasmic membranes of neoplastic cells. Although histologically similar, the tumors appeared heterogeneous as to their immunologic phenotype, with the majority demonstrating markers for T helper/inducer lymphocytes.

An antigen Leu M1 has been localized to myelomonocytic cells and Reed-Sternberg cells by light microscopic immunocytochemical studies. We used both pre- and post-embedding immunoelectron microscopy to define the ultrastructural distribution of this antigen. Post-embedding techniques heavily labeled the granules of polymorphonuclear leukocytes and the nonspecific granules of eosinophils. At high concentrations there was labeling of the specific granules of the eosinophil. The antibody consistently labeled the perinuclear granules and vesicles of Reed-Sternberg cells. Some Reed-Sternberg cells also exhibited labeling of the endoplasmic reticulum, suggesting that these cells have the capacity to synthesize this antigen. Although plasma membranes were labeled with the post-embedding technique, these structures were most heavily labeled with the pre-embedding method. These results indicate that Leu M1 is synthesized and packaged by Reed-Sternberg cells and represents an integral structural component of these cells.

The absence of keratin staining in tumor cells from localized fibrous mesotheliomas in both paraffin-embedded and frozen sections with sensitive peroxidase-antiperoxidase and avidin-biotin techniques is described. In addition ot the absence of staining for whole-stratum corneum keratin proteins, sections were negative for keratins of different molecular weights (45, 55, and 63 kilodaltons) that are characteristically present in mesothelial cells. Ultrastructurally, the cells most closely resembled mesenchymal cells of the fibroblastic type. These findings are in accordance with recent theories that relate the derivation of localized fibrous mesotheliomas to nonmesothelial cells, including subpleural connective tissue. Based on differences in immunohistochemical staining, the tumors appear to be unrelated to diffuse malignant mesotheliomas.

Human myocardium with focal myocytolysis (vacuolar degeneration, colliquative myocytolysis) was examined by routine light microscopy and by immunoperoxidase staining techniques for creatine kinase (CK) M and B, myoglobin, lactate dehydrogenase (H4)(LDH-1), and aspartate aminotransferase (AST, GOT). Sections of myocardium were selected from autopsy and surgical specimens from patients with and without clinical morphologic evidence of ischemic heart disease. Areas of coagulation necrosis showed loss of enzyme staining, while both normal and myocytolytic cells stained darkly. These results indicate that fibers with myocytolysis retain enzymes and other proteins, indicating sarcolemmal integrity, which is not present in fibers with coagulation necrosis. The implication of these findings is that fibers with myocytolysis are viable; thus, myocytolysis may be a reversible form of myocardial alteration that does not necessarily lead to cell death and eventual myocardial fibrosis.

Immunohistochemical staining for involucrin, a cytoplasmic protein synthesized during squamous maturation, was assessed in histologic sections from hysterectomy and cone biopsy specimens from patients with cervical neoplasia. In normal and condylomatous squamous epithelium, diffuse cytoplasmic staining was seen in the suprabasal layers, with no staining of the basal cells. Staining was absent in two cases of cervical intraepithelial neoplasia (CIN), grade III, in which the lesions were composed entirely of undifferentiated cells and markedly decreased in cases involving large numbers of basal cells. In 19 of 23 cases (83 per cent) of CIN, however, focal staining for involucrin was seen in large differentiated cells in the more superficial layers, and in two cases of keratinized CIN diffuse suprabasal staining was observed. Similarly, strong staining for involucrin was present in differentiated areas in one case of microinvasive squamous cell carcinoma and in 93 per cent of cases of infiltrating squamous cell carcinoma. These findings suggest that involucrin is a marker for maturation in cervical squamous epithelial neoplasms. Patterns of immunohistochemical staining for involucrin in keratinized dysplasia and differentiated squamous carcinomas should be taken into consideration if loss of involucrin staining is used as a criterion for neoplastic transformation of cervical epithelium, as has been proposed.

Sixty-four lung tumors were evaluated for the presence of immunoreactive neuron-specific enolase (NSE), bombesin (Bn), and chromogranin (Cg) to assess their value as markers for neuroendocrine cells in the histologic diagnosis of pulmonary neoplasms. Staining was correlated with the presence and density of neurosecretory granules (number of neurosecretory granules per unit cytoplasmic cross-sectional area) as determined by planimetry on electron micrographs. The cytoplasmic density of neurosecretory granules was significantly greater in the carcinoid tumors than in the small cell carcinomas (P less than 0.001). Neuron-specific enolase was localized in all of the neuroendocrine granule-bearing tumors but was also present in 57 per cent of the nonneuroendocrine carcinomas. Bombesin was present in 68 per cent of the neuroendocrine tumors and in less than 1 per cent of the nonneuroendocrine tumors. Staining for Cg appeared to correlate with the density of neuroendocrine granules, with staining in carcinoid tumors but no staining in small cell anaplastic carcinomas. A panel of antibodies may be required for the reliable identification of neuroendocrine lung tumors by immunohistochemical techniques.