Extragonadal germ cell tumors of the head and neck region: review of 16 cases

During the period from 1928 to 1982, 16 children were treated or seen in consultation at the Children's Hospital Medical Center for extragonadal germ cell tumors of the head and neck region. Collectively, these tumors accounted for only 5 per cent of all benign and malignant germ cell tumors. Fourteen tumors were diagnosed in newborns and were classified as pure teratomas, either mature or immature. Six of these tumors were located in the cervical region, three presented within superficial facial structures, two were retro-orbital, and three arose within oropharyngeal or nasopharyngeal tissues. There were three endodermal sinus tumors, one of which appeared in an 11-month-old child who had undergone incomplete resection of an oropharyngeal teratoma as a newborn. Endodermal sinus tumors presented within the oropharynx, nasopharynx, and floor of the mouth and affected children at older ages (6 to 11 months). The overall prognosis for infantile teratomas of the head and neck region (exclusive of brain and spinal cord) is excellent, despite the presence of immature elements; however, tumor-related deaths can result from large unresectable primary tumors. The prognosis for children with endodermal sinus tumors remains guarded, with successful management depending on early diagnosis and aggressive adjuvant therapy.     

Thymoma: lymphoid and epithelial components mirror the phenotype of normal thymus

Six thymomas were studied with monoclonal and polyclonal antisera and an immunohistochemical technique to characterize the lymphocytic and epithelial components of the tumor. The T lymphocytes had characteristics of thymocytes, and cortico medullary differentiation was demonstrated within all tumors, regardless of histologic appearance. Cortical thymocytes were positive with anti-terminal deoxynucleotidyl transferase, OKT6, and OKT10, all of which failed to stain medullary thymocytes. Conversely, A1G3 stained medullary thymocytes exclusively. Epithelial cells reacted with A2B5, an antibody that identifies cells of neuroendocrine origin. Epithelial cell processes were also positive with anti-p19, a monoclonal antibody directed against the internal protein of HTLV, which also reacts with normal thymic epithelium. No correlation was found in the distribution of epithelial cells with evidence of cortical and medullary thymocyte differentiation. However, the components of the tumor mirrored the normal cellular and structural components of the thymus.     

Cytogenetic studies in ovarian cancer

Cytogenetic studies of ovarian cancer have been conducted in the Medicine Branch, NCI, National Institutes of Health for 5 years. A total of 72 patients were studied by direct preparation and/or 1- to 3-day short-term culture of ascites (86 samples), pleural fluid (4 samples), and tumor (2 samples). Repeat examinations (1-24 months later) were performed in 7 of the 72 patients. Forty-four patients (62%) were successfully analyzed with banding techniques: 6 patients had adenocarcinoma, 7 had serous adenocarcinoma, 13 had serous papillary adenocarcinoma, 7 had serous papillary cystadenocarcinoma, 2 had mucinous adenocarcinoma, 6 had undifferentiated or poorly differentiated adenocarcinoma, 1 had clear cell adenocarcinoma, and 2 were not classified. Of these 44 patients, 29 had received prior chemotherapy, 14 were untreated, and in 1 patient the treatment status was unknown. Aneuploidy was observed in all patients and there was considerable variation in the chromosome numbers (even within single samples), often ranging from diploidy to triploidy to tetraploidy. All 44 patients had numerical abnormalities and 39 had structural abnormalities. The chromosomes most frequently involved in structural abnormalities (in decreasing order according to the number of patients involved) were #1, #3, #2, #4, #9, #10, #15, #19, #6, and #11; the least involved chromosomes were #21 and #5. Clone formation and the number of chromosomes involved in structural abnormalities increased with duration of disease and were more extensive in patients treated with chemotherapy than in patients treated with surgery alone. Our data did not show a deletion of chromosome #6 (6q-) to be specific for ovarian cancer.     

Cytologic detection of virus-specific DNA by in situ hybridization in syrian hamster embryo cells transformed by viral or combined chemical and viral treatment

A series of simian adenovirus 7 (SA7)-transformed Syrian hamster cell lines that had T antigen and produced tumors in neonatal hamsters were examined by radioautography in conjunction with in situ molecular hybridization to determine the extent to which the viral genome is integrated on specific chromosomes and the consequences of such integration on sister chromatid exchange (SCE) frequency. No consistent cytological or chromosomal localization of viral DNA in situ hybridization with viral complementary [³H]RNA was detected, even though all lines had an average of one or two viral genomes per cell by molecular hybridization. The SA7 DNA appears to be inserted randomly among the chromosomes and nuclei.     

A human ganglioglioma containing paired helical filaments

Neurofibrillary tangles composed of paired helical filaments were found in a human ganglioglioma. This is the first reported occurrence of neurofibrillary tangles in a neoplasm. These tangles were visible light microscopically with hematoxylin-eosin and Bodian's stains. They were confirmed as neurofibrillary tangles with Congo red staining under polarized light and with thioflavine S fluorescence. Untrastructurally, the tangles were composed of 10-nm filaments twisted in a helix with 80 nm between constructions. Thus, neoplastic proliferation does not preclude production of paired helical filaments. Cells grew from explants of this tumor, but no paired helical filaments were found in the cells examined. Two other gangliogliomas and normal brain tissue studies by the same procedures did not show paired helical filaments. Gangliogliomas that contain neurofibrillary tangles provide an alternative source of abnormal filaments for analysis.     

Abnormal beta adrenergic responsiveness in allergic subjects: analysis of isoproterenol-induced cardiovascular and plasma cyclic adenosine monophosphate responses

Beta adrenergic responses were compared between normal control subjects and patients with allergic asthma or allergic rhinitis and a group of asymptomatic individuals with positive immediate hypersensitivity skin tests. Two responses to infused isoproterenol were monitored: increases in pulse pressure and plasma cyclic adenosine monophosphate (cyclic AMP). Although the normal control subjects responded with increases in pulse pressure of greater magnitude than the other groups in response to infused isoproterenol, the differences in responsiveness were more apparent when the concentration of isoproterenol required to increase the pulse pressure ≧22 mm Hg was compared. The 25 control subjects required 8.04 ± 0.48 ng/kg/min isoproterenol, whereas the 17 asthmatic patients required 14.25 ± 1.21 (p < 0.0001), the eight subjects with allergic rhinitis required 12.75 ± 1.58 (p < 0.0005), and the seven asymptomatic subjects with positive skin tests needed 11.1 ± 1.26 (p < 0.01). Comparison of baseline plasma cyclic AMP levels of the groups revealed no apparent differences. However, the normal controls responded to isoproterenol with larger increases in plasma cyclic AMP than the other groups at both 6 and 9 ng/kg/min. Furthermore, significantly fewer of the subjects with asthma, rhinitis, or positive skin tests demonstrated an increase in plasma cyclic AMP ≧ 50% above baseline as compared with controls. Thus, as reflected in both cardiovascular and cyclic AMP responses to infused isoproterenol, allergic asthmatic subjects are hyporesponsive as compared with normal controls. However, a comparable degree of diminished responsiveness is seen in subjects with allergic rhinitis or in asymptomatic individuals with positive skin tests. Therefore beta adrenergic hyporesponsiveness appears to be related with the atopic state rather than with asthma.     

Histologic assessment of lymph nodes in mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma): clinical correlations and prognostic import of a new classification system

Mycosis fungoides and the Sézary syndrome share common cutaneous histopathologic features, and this spectrum of malignant disease is referred to here as cutaneous T-cell lymphoma (CTCL). A method (LN classification) for describing the histopathologic features of lymph nodes in CTCL is presented. In this system, lymph node biopsy specimens are scored according to the number of atypical lymphoid cells in T-cell-dependent paracortical zones and the preservation or distortion of the lymph node architecture. Lymph node architecture is preserved in lymph nodes scored LN1 to LN3, and these nodes may have coexistent dermatopathic change. LN1 nodes have single infrequent atypical lymphocytes in paracortical T-cell regions. LN2 nodes have small clusters of paracortical atypical cells. LN3 nodes have large clusters of atypical cells. LN4 nodes are partially or totally effaced by atypical cells. This system was used to classify 96 lymph node biopsy specimens obtained within six months of the initial diagnosis of CTCL; no LN1 nodes, 37 LN2, 44 LN3, and 15 LN4 nodes were found. The LN class was significantly correlated with the extent of skin, blood, and visceral involvement, as well as with survival. Patients with LN2 lymph nodes have an estimated five-year survival of 70 per cent, while patients with LN3 and LN4 nodes have estimated five-year survivals of 30 and 15 per cent, respectively. The survival differences between the LN subgroups were all significant (P less than 0.05). The LN classification system was clearly shown to be reproducible among experienced pathologists. The LN system for the histopathologic classification of lymph nodes in CTCL is of prognostic value and should be used to assess lymph node biopsies in patients with CTCL.     

Autologous Rosette-forming T Cells (ARFT) regulate responses of T cells

In the previous paper of this series, we reported that T cells forming rosettes with antologous erythrocytes (ARFTs) regulated primary proliferative responses of nonrosette-forming T cells (NRFTs) to TNP-modified autologous non-T cells and to allogeneic non-T cells.In the present paper, we investigated the cytotoxic responses of unfractionated T cells (UTs), ARFTs, and NRFTs against TNP-modified autologous cells and against allogeneic cells after in vitro culture with TNP-modified non-T cells (TNP-auto-MLR) or with allogeneic non-T cells (allo-MLR). After 1 week in an allo-MLR, cytotoxic T cells were generated from the NRFT fraction. Almost the same degree of cytotoxicity was observed in UTs undergoing an allo-MLR; least cytotoxicity was observed in the ARFT fraction. In contrast, only minimal cytotoxic activities against TNP-modified autologous cells were generated from UTs and ARFTs after TNP-auto-MLR. However, significantly stronger cytotoxic activities were demonstrated against TNP-modified autologous cells when the ARFTs were removed, and the remaining NRFTs were used as the responder in the TNP-auto-MLR.It was concluded that the NRFT fraction contained most of the primary precursors for both hapten-reactive and alloreactive killer cells, as well as lymphocytes helping the formation of cytotoxic effector cells.If UTs were separated into ARFTs and NRFTs after a TNP-auto-MLR, these fractions demonstrated equal degrees of cytotoxicity toward TNP-modified autologous cells. However, the addition of ARFTs to NRFTs at the beginning of such a culture inhibited both proliferative and cytotoxic responses of the NRFTs to TNP-non-T cells. Finally, if ARFTs were added prior to a cytotoxic assay mediated by NRFTs, no inhibition was observed. Taken as a whole, our data suggest that ARFTs appear to act during the mixed lymphocyte reaction to block the development of cytotoxic cells.     

Fiber counting and analysis in the diagnosis of asbestos-related disease

Analysis of numbers and types of asbestos fibers present in lung tissue may provide insights into the pathogenesis of asbestos-induced disease, as well as diagnostic information concerning the relationship of a given lesion to asbestos exposure. This type of analysis requires extraction of fibers and asbestos bodies from lung tissue, preferably by means of a digestion-and-concentration technique, and examination with a combination of electron optical techniques, including electron diffraction and energy-dispersive x-ray spectroscopy. The combination permits definitive identification of asbestos fibers. Asbestos bodies have been shown to contain asbestos no matter what population they are found in, but they appear to be of value in ascertaining unusual exposure only when present in very large numbers. Numbers of asbestos bodies markedly underestimate total numbers of fibers present in lung. In patients from the general population, the mean number of asbestos fibers is about 1 X 10(6)/g dry lung; of this number, more than 80 per cent are fibers of chrysotile less than 5 microns long. Patients in the general population who have pleural plaques have about the same total number of fibers, but their lungs contain about a 50-fold increase in long thin amphibole fibers of commercial origin. Patients who have asbestosis and most patients who have mesothelioma have 100 to 200 X 10(6) fibers/g dry lung; the grade of asbestosis appears to be related to total fiber content. Occasional patients may develop mesotheliomas with much smaller fiber burdens. Both benign and malignant pleural diseases appear to be closely related to the presence of long thin amphibole fibers. Analysis of pulmonary fiber burden suggest that asbestos-related disease is not merely a matter of total numbers of fibers present, but that factors such as fiber type and size are equally important.     

The effects of histamine and prostaglandin D2 on rat mast-cell cyclic AMP and mediator release

The possibility that histamine may play a functional role in modulating mast-cell secretion, as has been suggested for basophil degranulation, has both physiologic and pharmacologic implications. Therefore the capacity of histamine to influence rat peritoneal mast-cell (RPMC) cyclic AMP levels and reversed anaphylatic degranulation as reflected in the release of 3H-serotonin (5-HT) was examined. To ascertain that RPMC were functionally responsive to exogenous hormonal stimulation, assessment of prostaglandin (PG) D2 effects on cyclic AMP and 5-HT release were determined in parallel. Although PGD2 (100 microM) increased cyclic AMP and inhibited 5-HT release in the presence of 50 microM aminophylline, histamine (up to 1000 microM) was ineffective was ineffective in both. However, 1000 microM histamine in the presence of 500 microM aminophylline was capable of transiently increasing RPMC cyclic AMP (for 15 to 30 sec) and under these conditions of suppressing 5-HT release. The receptor subtype involved in the suppressive actions of histamine appeared to be of the H-1 type as reflected in the capacity of specific H-1 agonists to reproduce the inhibition of 5-HT release, whereas neither H-2 agonists nor H-2 antagonists had any influence. Thus, under conditions in which phosphodiesterase enzymatic action is impaired, histamine in extremely high concentrations is able to modulate mast-cell secretion. However, it seems very unlikely that this action of histamine has any physiologic significance.     

ADCC analysis with the Coulter counter: a highly sensitive, ultramicro assay suitable for clinical and experimental application

Antibody-dependent cellular cytotoxicity (ADCC) is an in vitro immune mechanism implicated in several in vivo phenomena such as transplant rejection, tumor immunity and parasite elimination. We developed a method for detecting ADCC using the Coulter Counter and the Coulter Channelyzer that circumvents many of the disadvantages associated with existing assays for ADCC. Effector mononuclear cells were incubated with chicken red blood cell (CRBC) targets and anti-target antibody for 1-1, 5h. Killing was quantified by the Coulter Counter on the basis of size differences between effector and target cell nuclei. Using a 4 microliter total volume we were able to detect cytotoxic levels of 55% when as few as 5000 effector cells were incubated with an equal number of target cells. This method for the detection of ADCC may be suitable for clinical and research application.     

Creatine kinase subunits M and B as markers in the diagnosis of poorly differentiated rhabdomyosarcomas in children

Antibodies against the M and B subunits of creatine kinase were assessed for their usefulness in the diagnosis of poorly differentiated rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin-biotin-peroxidase complex technique were used. The majority of the poorly differentiated and all of the moderately and well-differentiated rhabdomyosarcomas studied showed immunostaining for the M subunit. The rhabdomyoblastic component of malignant "triton" tumors was also positive. Staining, although weak compared with that of the rhabdomyosarcomas, was also observed in a few leiomyosarcomas, hemangioendotheliosarcomas, malignant fibrous histiocytomas, and ganglioneuroblastomas. On the other hand, staining for the B subunit was seen in many types of soft tissue tumors, including rhabdomyosarcoma, Ewing's sarcoma, and (ganglio)neuroblastoma. The results indicate that creatine kinase subunit M is a useful marker for distinguishing poorly differentiated rhabdomyosarcoma from other types of small round cell tumors in children, such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma.