In situ polymerase chain reaction-based localization studies support role of human herpesvirus-8 as the cause of two AIDS-related neoplasms: Kaposi's sarcoma and body cavity lymphoma.

Several lines of investigation point to a new herpesvirus, human herpesvirus-8 (HHV-8), as the cause of two different neoplasms seen in AIDS patients-Kaposi's sarcoma (KS) and body cavity B cell lymphoma. If this virus is the etiological agent, rather than another opportunistic infectious agent, it should be present in the earliest detectable clinical lesions on a temporal basis, and localize to specific target cells in a spatial pattern consistent with tumorigenic pathways. In this study, we take advantage of the clinical accessibility to biopsy early (patch stage) skin lesions of KS to address the temporal issue, combined with in situ PCR and dual immunostaining using a marker identifying malignant cells, to address the spatial localization issue. 21 different tissue samples were subjected to PCR analysis and in situ PCR with and without simultaneous immunostaining. In normal skin from healthy individuals, no HHV-8 DNA was detected by PCR or in situ PCR. However, in all PCR-positive tissues, distinct and specific in situ PCR staining was observed. In four different patch stage KS lesions, in situ PCR staining localized to nuclei of endothelial cells and perivascular spindle-shaped tumor cells. Later stage KS lesions (plaques and nodules) revealed additional positive cells, including epidermal keratinocytes (four of five), and eccrine epithelia (two of four). These patterns were nonrestricted to skin, as pulmonary KS also revealed HHV-8-specific infection of endothelial cells and KS tumor cells, as well as epithelioid pneumocytes (two of two). In body cavity B cell lymphoma by dual staining, HHV-8 was present in malignant tumor cells (EMA immunostained positive) and not in reactive lymphocytes. These results reveal an early temporal onset and nonrandom tissue and cellular distribution pattern for HHV-8 infection that is consistent with a causal link between this DNA virus and two AIDS-related neoplasms.     

Benign Idiopathic versus Mycosis-Fungoides-Associated Follicular Mucinosis

A study was undertaken in an attempt to identify useful histologic criteria that may allow differentiation between benign idiopathic and mycosis-fungoides-associated follicular mucinosis. We chose young patients because no person under 20 years of age with coexisting follicular mucinosis and mycosis fungoides disease has ever been reported. Our three most important observations in benign juvenile idiopathic follicular mucinosis were as follows: The lymphocytic infiltrate was generally confined to follicular, perifollicular, or perivascular zones with no extension of either normal or atypical mononuclear cells into the epidermis or into papillary/reticular dermis. Within follicular epithelium there were dense collections of lymphocytes with occasionally atypical-appearing nuclei in three of the eight patients, but never as Pautrier microabscesses. There was absence of a significant associated plasma cell or eosinophil-containing inflammatory dermal infiltrate. These findings are in contrast to those of older patients with follicular mucinosis and mycosis fungoides.     

Analgesic nephropathy

Many questions about analgesic nephropathy (AN) lack clear-cut answers. We present available evidence for and against proposed answers to many of these questions. These include: (1) Is acetaminophen (AC) nephrotoxic when taken as the sole analgesic? (2) Is the combination of acetylsalicylic acid (ASA) and AC more nephrotoxic than AC taken alone, and if so, why? (3) What are the minimum doses and durations of ingestion required to produce analgesic nephrotoxicity? (4) Is the combination of ASA and AC (a major metabolite of phenacetin) less nephrotoxic than that of phenacetin and ASA combined? (5) Does caffeine in combination with analgesics contribute to nephrotoxicity? (6) What is the incidence of end-stage renal disease (ESRD) due to AN? (7) What uniform diagnostic criteria should be established for AN? (8) What are the earliest anatomic and biochemical abnormalities? (9) What are the mechanisms of renal injury? (10) Does AC cause uroepithelial neoplasia? (11) What research might be most beneficial? Based mainly on associations, some strong, we suggest that AN still exists as a cause of ESRD in the United States, where AC/ASA combinations are available over the counter, and in Canada, where they are not. We also suggest that the evidence needed to recommend that the AC/ASA combination be excluded from over-the-counter analgesic preparations still has limitations. A prospective multicenter study comparing incidence related to AC/ASA in the United States and to AC in Canada and the United States may be needed to answer this question. For such a study to be worthwhile, an adequate incidence in both countries is required.     

Radiologic diagnosis of oat cell cancer in a high-risk screened population

A screening program of 10,040 cigarette-smoking men over 45 years of age was undertaken in an attempt to achieve earlier diagnosis, thereby increasing the cure rate, of oat cell lung cancer. Of the 155 men who were found to have lung cancer, 27 (17%) had confirmed oat cell cancer. Only one case was diagnosed at the first examination. The other 26 cases (called incidence cancer) were diagnosed by subsequent examinations. In 24 of the 26 patients, the tumor was not found until it was advanced (Stage III), and of these patients, only one is alive at 21 months follow-up. Two tumors were diagnosed as oat cell carcinoma at an early stage (Stage I), and both patients are alive with no evidence of disease at seven and 24 months. The screening program used in this study did not succeed in detecting oat cell cancer at an early stage.     

Oral submucosal dendrocytes: factor XIIIa+ and CD34+ dendritic cell populations in normal tissue and fibrovascular lesions

Factor XIIIa+ and CD34+ dendritic cells, believed to be subsets of monocyte/macrophages, have been identified in dermis and in dermal tumors. The purpose of this study was to determine the presence and distribution of analogous cell types in oral submucosa and oral fibro-vascular lesions. Antibodies to XIIIa, CD34, S-100 protein, and macrophage antigen (MAC 387) were tested on formalin-fixed, paraffin-embedded tissue sections from normal mucosa, peripheral fibroma (PF), peripheral ossifying fibroma (POF), peripheral giant cell granuloma (PGCG), pyogenic granuloma (PG), lymphangioma (La), benign fibrous histiocytoma (BFH), idiopathic histiocytosis (IH), angiofibroma (Af) using an ABC immunoperoxidase technique. Numbers of positively stained cells were compared to unstained cells in the tumors. XIIIa positive submucosal dendrocytes (CD34-, S-100-, MAC 387-) were found in abundance in normal tissue in characteristic distributions: collagen-associated, vessel-associated, and lymphoid-associated. The percentage of XIIIa+ cells in the oral tumors was as follows: PF: 10-30%, POF: 5-10%, PGCG: 0-5%, PG: 5-20%, La: 0%, BFH: 5-25%, IH: 0%, and Af: 10-20%. CD34+ dendrocytes (XIIIa-, S-100-, MAC 387-) were few in number and were found in deeper submucosa, especially around skeletal muscle. Other than blood vascular endothelium, CD34+ cells were not generally seen in the oral tumors studied. It is concluded that two previously unrecognized dendrocyte populations reside in normal submucosa. XIIIa+ cells participate in the formation of some oral reactive and neoplastic lesions.     

Lymphoepitheliomalike carcinoma of the skin. A case report with immunophenotypic analysis and in situ hybridization for Epstein-Barr viral genome.

Lymphoepithelioma is a malignant epithelial neoplasm of the nasopharynx. Similar malignancies--lymphoepitheliomalike carcinomas--of salivary glands, thymus, larynx, lung, stomach, and uterus have been described. We present here a case of lymphoepitheliomalike carcinoma of the skin in an 84-year-old woman. Histologically this neoplasm presented as a fairly discrete dermal aggregate of syncytial nests of epithelioid-appearing cells that displayed no squamous or glandular differentiation, surrounded by a dense lymphocytic infiltrate. Results of immunophenotypic studies showed expression of high molecular weight cytokeratins and increased density of dermal dendrocytes within and adjacent to the tumor. No Epstein-Barr viral genomic sequences were detected by in situ hybridization, which suggests that cutaneous neoplasms may have different etiologic agents compared with similar tumors, found to be associated with this DNA-containing virus, arising in extracutaneous sites. The combined light microscopic and immunohistochemical assessment of this rate cutaneous neoplasm permits distinction of lymphoepitheliomalike carcinoma from benign/malignant lymphoproliferative disorders or neuroendocrine carcinomas.     

Correlating magnetic resonance imaging with the biochemical content of the normal human intervertebral disc.

Magnetic resonance imaging was used to determine the T2 relaxation times of prepared proteoglycan solutions and of normal human intervertebral disc tissue from the annulus fibrosus (AF) and nucleus pulposus (NP). The collagen, proteoglycan, and water contents of the disc tissue samples were determined by biochemical assays after they were scanned. Correlations among 1/T2, collagen, proteoglycan, and water contents of the tissue samples and among 1/T2, water, and proteoglycan contents of the proteoglycan solutions were calculated. A moderate negative correlation between 1/T2 and water content was noted for the tissue samples, and a very high negative correlation was found between 1/T2 and water content for the proteoglycan solutions. The very high positive correlation between 1/T2 and proteoglycan content of the proteoglycan solutions is probably due to this negative correlation between 1/T2 and water content. There was no significant correlation between 1/T2 and proteoglycan content of the tissues. The moderate positive correlation between 1/T2 and collagen content is probably due to the high negative correlation between collagen content and water content. No significant correlation was found between the collagen and proteoglycan contents of the tissues. Thus it appears that the data confirm previous reports in the literature that the collagen of the disc tissue functions to control its water content.