Nucleolar organizer regions in paragangliomas of the head and neck.

The clinical behavior of head-and-neck paragangliomas cannot be accurately predicted using standard histologic criteria. Immunohistochemical profiles have proved to be prognostically helpful; however, other independent indicators of prognosis are needed. Tissue markers of proliferative activity include argyrophilic nucleolar organizer regions (AgNOR), which are proteins specifically associated with loops of transcriptionally active ribosomal DNA. Fifteen paragangliomas of the head and neck were divided into solitary nonrecurrent (n = 8), recurrent or locally invasive (n = 4), and multiple (n = 1), or malignant (n = 2) groups. The mean AgNOR count per cell was statistically different between the solitary nonrecurrent and the combined other poorer prognosis groups, suggesting that it may be useful as an independent indicator of biologic behavior. The wide variation in AgNOR counts within groups and the overlap of counts between groups limit, however, the predictive value of this technique for individual tumors.

A review of the histology, ultrastructure, immunohistology, and molecular biology of extra-adrenal paragangliomas.

This review summarizes our understanding of extra-adrenal paragangliomas, a subject that has evolved considerably during the past several years. Our object was to review the anatomical, histologic, and biological features of normal and neoplastic glands, with emphasis on immunohistologic studies, and briefly discuss the potential application of nucleic acid hybridization. Since it is difficult to predict clinical outcome for patients with paragangliomas, we have emphasized the differences between benign and malignant paragangliomas, concentrating on recent results obtained using immunohistologic techniques. These studies have emphasized the critical importance of the identification, by immunohistologic means, of two distinct cell populations, chief cells (type I) and sustentacular cells (type II). The relationship between these two cell populations, stable in normal glands and benign tumors, is progressively lost in tumors of increasing degrees of malignancy, sustentacular cells being absent from the most progressively metastasizing paragangliomas.

Paragangliomas: assessment of prognosis by histologic, immunohistochemical, and ultrastructural techniques.

To predict clinical outcome, we studied 42 paragangliomas from 37 patients by routine histology, immunohistochemistry, and electron microscopy. A panel of antisera to neuron-specific enolase (NSE), chromogranin, and met-enkephalin was used to identify chief (type I) cells, and S-100 protein and glial fibrillary acid protein (GFAP) sustentacular (type II) cells. The intensity of staining of type I cells and the density of type II cells were assessed semiquantitatively (0 to 4+) in a total of 38 tumors. A total of 23 of 24 low-grade tumors (solitary, multiple, or associated with other neoplasms; 95.8%) contained type II cells immunoreactive with either S-100 protein or GFAP, and all were positive when S-100 protein and GFAP were used in combination. Five of the nine intermediate-grade (recurrent and/or locally aggressive) tumors were identified as glomus jugulare tumors (GJT). Three intermediate-grade GJTs were devoid of GFAP-reactive type II cells and four GJTs were negative for S-100 protein. Type II cells were identified in only one of five high-grade (malignant) paragangliomas and that tumor contained vanishingly rare cells that were weakly S-100 protein positive but GFAP negative. Sustentacular cell density and chief cell staining intensity were both inversely related to tumor grade. The most sensitive chief cell marker was NSE (92.1%), followed by chromogranin (84.2%). The least sensitive (73.0%) and specific marker was met-enkephalin. Combinations of NSE or chromogranin with met-enkephalin identified chief cells in all cases. Electron microscopy identified neurosecretory granule-containing chief cells, but was of less value in delineating sustentacular cells because of their scarcity and the absence of specific features. By comparison, immunohistochemistry was superior in identifying sustentacular cells. The use of an immunohistochemical panel, in addition to routine histology, can confirm the diagnosis of a paraganglioma and can give an indication of the likely prognosis for a patient.

Prevalence of antibodies to HTLV-III in quality-assurance sera.

We tested 146 clinical-laboratory quality-assurance sera for antibodies to human T-lymphotropic virus III (HTLV-III). Of 127 human-based samples, 39 (31%) were positive by an immunoenzymometric assay (IEMA). Samples of human origin that gave IEMA reactivity included four of 10 ethylene glycol-based (liquid) samples, two of six in-house pools of fresh sera, and 32 of 111 lyophilized samples. All 19 bovine-based samples were negative. Antibodies to HTLV-III in 16 samples were remeasured by a second IEMA and the Western blot technique. All assays detected antibody reactivity in four of the 16 samples; however, results of the second IEMA and the Western blot agreed best. We report large discrepancies between assay results when laboratory reagents are tested for HTLV-III antibodies, and find that many quality-assurance samples containing human sera have measurable IEMA reactivity for HTLV-III antibody. Reactivity in these assays indicates the presence of antibody, not viral infectivity.