Detection of Epstein-Barr virus genome in sinonasal undifferentiated carcinoma by use of in situ hybridization.

Associations between Epstein-Barr virus and undifferentiated carcinomas of nasopharynx, parotid gland, and thymus have recently been reported. Epstein-Barr virus has also been associated with malignant lymphoma of the nose and paranasal sinuses. These findings raise the possibility that Epstein-Barr virus may additionally be linked to undifferentiated carcinoma of the nose and paranasal sinuses (SNUC), an uncommon but distinctive and highly aggressive neoplasm. Histologically, SNUC consists of small and medium cells, the precise characterization of which often requires immunocytochemical analysis. This study investigates the presence of DNA sequences of Epstein-Barr virus in biopsy specimens of 13 cases of SNUC that were defined immunocytochemically by use of previously reported criteria. In situ hybridization was used to detect Epstein-Barr virus genome in different cell types in routinely processed, paraffin-embedded tissues. Epstein-Barr virus-specific DNA sequences were detected in tumor cells of SNUC specimens from 5 of the 13 cases examined. No correlation was found between positive hybridization and primary tumor site, morphologic subtype, or disease course. Epstein-Barr virus DNA was detected in 38% (5 of 13) of the SNUC samples analyzed. This finding suggests that this virus may play a role in the pathogenesis of this rare neoplasm.

Interleukin-6 and acute-phase proteins in head and neck cancer.

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), alpha 1-antitrypsin (ATT), alpha 1-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.

Interleukin-1 beta and interleukin-6 release by peripheral blood monocytes in head and neck cancer.

In patients with advanced head and neck squamous cell carcinoma (HNSC), evidence of cell-mediated immunity and monocyte functional abnormalities has been reported. We studied the production of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by peripheral blood monocytes from 22 patients with HNSC (12 larynx and ten oral cavity cancers) in comparison with monocyte cytokine production of age-matched healthy subjects. Pure monocytes were incubated with and without lipopolysaccharides (LPS) (10 micrograms ml-1) for 4 h at 37 degrees C and IL-1 beta and IL-6 concentrations were determined in supernatants by specific ELISA. There was no significant difference in IL-1 beta levels in monocyte supernatants from cancer in comparison to control subjects; conversely, a higher IL-6 production by unstimulated and LPS-activated cells from HNSC patients than from controls was found. No relationship was observed between cytokine production and cancer stage. The regression analysis evidenced a significant correlation between IL-1 beta and IL-6 monocyte-release in HNSC patients and in controls, so suggesting a possible autocrine control of IL-6 production by other cytokines.

Monocyte tumor necrosis factor production in head and neck squamous cell carcinoma.

Changes in monocyte and macrophage function have been demonstrated in patients with head and neck squamous cell carcinoma. The purpose of this study was to evaluate tumor necrosis factor (TNF) production by activated monocytes from patients with head and neck squamous cell carcinoma and to evaluate its relation to cancer stage, weight loss, and performance status. Monocytes from patients (n = 10) and controls (n = 10) were isolated from peripheral blood mononuclear cells by plastic adherence and incubated with lipopolysaccharide (10 micrograms/mL). The TNF concentration of supernatants was assayed by TNF alpha-specific immunoassay. The TNF production by monocytes from head and neck squamous cell carcinoma patients was significantly higher (P less than .001) than those of controls. No significant relationship was found to cancer stage, weight loss, and performance status. These findings indicate that, in head and neck squamous cell carcinoma patients, an increased TNF production by activated monocytes takes place which does not correlate with cancer stage, cancer-related weight loss, and performance status.

Langerhans cells related to prognosis in patients with laryngeal carcinoma.

Intratumoral and peritumoral infiltration of T-zone histiocytes, mainly of mature Langerhans cells, was investigated in 88 patients with squamous cell carcinoma of the larynx by immunohistochemical methods using polyclonal antibodies against S100 protein and lysozyme. Granulocytic and lymphoid inflammatory infiltration and its relationship to the presence of Langerhans cells were also evaluated. Langerhans cells were present within the cancer tissues and showed a relationship with lymphoid infiltrate. No significant correlation was present among the density of Langerhans cells and the site of neoplastic growth (supraglottic or subglottic), granulocytic inflammatory infiltration, histological tumor grade, or clinical stage. Patients with high or intermediate density of Langerhans cells survived longer than those with low density (mean survival, 61%, 62%, and 0%, respectively). The number of Langerhans cells was relevant in patients with evident infiltration of lymphocytes and plasma cells, according to their ability to present antigens to sensitized T cells. Our results indicate that the presence of high or intermediate density of Langerhans cells and of marked lymphoid inflammation may be considered favorable prognostic factors for patients with squamous cell carcinoma of the larynx.

Labeling index in squamous cell carcinoma of the larynx.

Two cell kinetic parameters, the 3H-thymidine labeling index (TLI) and the mitotic index (MI), were studied in vitro on fragments of squamous cell carcinoma tissue of the larynx. They were evaluated to identify those elements able to characterize the growth of these solid tumors. The values of these parameters were analyzed as a function of the clinical stage and the involvement of the regional lymph nodes. Results showed a statistically significant increase in the TLI from stage T1 to T3. No statistically significant differences in the TLI values were observed between the patients with positive and negative lymph nodes.

Correlations between histopathological and biological findings in nasopharyngeal carcinoma and its prognostic significance.

Forty-five consecutive cases of nasopharyngeal carcinoma were morphologically and immunocytochemically studied using monoclonal (anti-B and anti-T cell) and polyclonal (anti-S100 protein and antilysozyme) antibodies with the peroxidase-anti-peroxidase method to identify infiltrating lymphocytes (T and B cell) and histiocytes (monocytic/macrophagic and dendritic cells) in nasopharyngeal carcinoma. A variable density of dendritic cells was found within the tumor nests in 22 (49%) of 45 nasopharyngeal carcinomas examined; infiltrating macrophages were demonstrated in 15 (33%) specimens and around the tumor in almost all cases. Cases with moderate or marked density of dendritic cells (S100+) survived longer than those without such infiltration (mean 5-year survival rates of 31%, 55%, or 64% in patients with absent, moderate, or marked densities, respectively; P less than 0.05). A significant relationship between monocytic/macrophagic cells (lysozyme+) within the tumor and survival was also found (mean 5-year survival rate of 27% or 61% in patients with absent, moderate, or marked densities, respectively). However, lymphocytic infiltration was not statistically related to a better survival. Analyzing lymphocytic infiltration, we found a large prevalence of T cells in the neoplastic tissue without any prognostic significance. These data were correlated to different histological subtypes according to the principal histological classifications of nasopharyngeal carcinomas (Micheau, et al.; World Health Organization; Cologne University) to individualize the scheme which correlates best with prognosis and biological features of nasopharyngeal carcinomas. Our data suggest that, considering dendritic cells and macrophages within cancer nests, nasopharyngeal carcinoma histiotypes can be correlated to patient prognosis.

Prognostic significance of accessory cells and lymphocytes in nasopharyngeal carcinoma.

Forty-five consecutive biopsy specimens of nasopharyngeal carcinoma (NPC) and 10 biopsies of healthy nasopharyngeal mucosa obtained from non-cancer patients were investigated by immunohistochemical methods. Monoclonal (B2, T1) and policlonal antibodies (against S-100 protein and lysozyme) with reference to infiltrating lymphocytes and accessory cells (monocytic/macrophagic and dendritic cells) were used. Variable population densities of dendritic cells (S100+) were demonstrated in 22 out of the 45 cases (49%) of NPC; the distribution of these cells was typically within the cancer nests. Monocytic/macrophagic cells (Lys+) were found along the tumor margins and interspersed among the tumor cells in 14 out of 45 (31%) cases. No significant statistical correlation between density of accessory cells and histological type of NPC (classified according to Micheau criteria) was found. Cases with a moderate to marked density of dendritic and monocytic/macrophagic cells survived longer than those with a slight one (mean survival of 63%, 67% and 29%, 27% respectively). In NPC tissues T-lymphocyte infiltration was prevalent. In contrast, B cells were numerous and T cells rare in normal control tissues. The intensity of T-cell infiltration was significantly high in cases with a marked density of S-100+ cells, according to the ability of these cells to present antigens to sensitized T-cells. This study suggests a prognostic significance for reactive cells infiltrating NPC, which means longer survival for cases associated with marked infiltration density of accessory cells.

[Histopathological parameters and lymphatic metastasis in supraglottic laryngeal carcinoma]. / Parametri istopatologici e metastatizzazione linfonodale nel carcinoma laringeo sopraglottico.

Histopathologic parameters in predicting lymph node metastasis of supraglottic laryngeal carcinoma. A systematic clinical-pathological study was performed on fifty-three resected cases of supraglottic laryngeal squamous cell carcinoma, followed up for at least 5 years. The aim of the research was to evaluate histopathologic parameters in predicting lymph node metastasis (N+) as expression of biological malignancy of the neoplasm. The following neoplastic microscopical features were studied: histopathologic and cytologic grading, pattern of growth, peritumoral inflammatory infiltrate, stromal reaction, tumoral necrosis. The results are as follows: stromal reaction and cytologic grading are not useful to identify N+ and N- cases. Cases with high and low degree of differentiation (Broder's grading) are significantly correlated respectively to low (14.3%) and high (70%) incidence of lymph node metastasis (p less than 0.03). A clear correlation is present between the pattern of growth "pushing" and lacking of node metastasis (84.6%). A favorable prognosis significance seems to be linked with the presence of peritumoral lymphoplasmocytic infiltrate, which results to be a marker of cases in which lymph node metastasis incidence is very low (5.5%; p less than 0.001). On the contrary lymph node metastasis incidence increase when tumoral necrosis is present (76.5%; p less than 0.001).

[Tumors of the lateral parapharyngeal space. Our case series]. / I tumori dello spazio parafaringeo laterale. Nostra casistica.

After a review of the literature, the authors present 20 cases of parapharyngeal tumors which were operated on over the past 13 years at the ENT Clinic of the University of Florence. Although diagnosis is generally made quite late, great improvement has been achieved with the new "imaging" techniques. New and better information has made it possible to choose the most suitable surgical approach. In such cases neoplasm is most frequently observed in young adults; they prove benign in most cases and are of varying oncotypes--most often of a salivary gland or neurogenic origin. Diagnosis is performed by a CT scanner with an intravenous contrast medium and by angiography of the carotid artery. More recently CT sialography and MRI have also been used. The surgical technique (transoral, transcervical, transparotid and transmandibular excision, alone or combined) was chosen according to localization, size and vascularity. Follow-up data show a high incidence of recovery (85%) with acceptable functional results.

T lymphocytes from tonsil and peripheral blood show different cytolytic and helper activities.

T lymphocytes from tonsil (To) and peripheral blood (PB) of 4 tonsillectomized children were subjected to clonal expansion with PHA in order to analyze at single cell level their cytolytic activity and their ability to produce interleukins such as IL-2, IFN-gamma and IL-4. Analyzing all T-cell clones (CD4+ and CD8+) obtained from To in comparison with those from PB, a reduced proportion of cells with lectin-dependent cytolytic activity (LDCC) (25% vs. 42%, p less than 0.01) and natural killer (NK) activity (18% vs. 31%, p less than 0.02) was found. These differences were proportionally related to the lower number of CD8+ T-cells in To than in PB. The proportion of CD4+ clones able to produce IL-2 and/or IL-4 were higher in To (75% and 61%) than in PB (52% and 25%, p less than 0.001 and p less than 0.001, respectively). In contrast, the proportion of CD4+ clones able to produce IFN-gamma was similar (53% and 58%) in both series of clones. According to the patterns of lymphokine synthesis, tonsillar T-cells differed from PB T-cells as follows: 1) the number of Th1-like CD4+ clones producing IL-2 and/or IFN-gamma (but not IL-4) were 23% vs. 44% in PB (p less than 0.001); 2) there was no difference between To and PB in the proportion of CD4+ clones producing IL-4 alone (Th2 clones: 9% vs. 8%); 3) CD4+ clones synthesizing IL-2, IL-4 and IFN-gamma at the same time were more frequent in To than in PB (Th3 clones: 53% vs. 17%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Intracranial post-traumatic aneurysm of the internal carotid artery as cause of epistaxis: considerations on 2 cases]. / Aneurisma post-traumatico intracranico della carotide interna come causa di epistassi: considerazioni su due casi.

Aneurysm of the internal carotid artery is rarely mentioned as a cause of epistaxis. This condition is quite rare but it is important to consider aneurysms in the etiology of epistaxis because of their high mortality rate and since they require management quite different from that of epistaxis of other origins. After arteriosclerosis the most frequent cause of an aneurysm of the internal carotid artery is a closed or penetrating craniofacial trauma injuring the artery. This leads to subsequent aneurysmal dilation of the cavernous and petrous portions of the artery itself. Aneurysms of the cavernous portion of the artery are more frequent. In this location the aneurysm has a close anatomical relationship with the sphenoid sinus as well as the nasal fossae. In the present paper two cases of traumatic intracavernous carotid aneurysms presenting epistaxis are described. In the first case, reported 25 years ago, the diagnosis was made on an autoptic table in young man who died after two severe episodes of massive nasal hemorrhage. The second case involved a 17-year-old man with a severe epistaxis reported one month after a close craniofacial trauma. An intracranial carotid pathology was suspected because of the recurrence of nose-bleeding and the history of reduced visual activity. Therefore angiography was performed which revealed a small aneurysm of the intracavernous segment of the left internal carotid artery. Subsequently, an endovascular balloon embolization of the aneurysm was successful, preserving the parent artery. The importance of considering aneurysms in the differential diagnosis of massive epistaxis is emphasized.

Analysis of 185 submandibular gland excisions.

A review of 185 submandibular gland excisions over a ten year period is presented. The symptoms, physical findings, diagnosis on pathological examination and prognosis have been noted in each case to determine the incidence of neoplastic versus non-neoplastic disease. In our series non neoplastic disease of the submandibular gland was found in 141 patients (76%) with a large predominance of inflammatory lesion, while only 26 patients (14%) had a neoplastic lesion (6 benign lesions and 20 malignant tumors). There were also 18 (10%) patients surgically treated with gland excision for a glandular metastatic involvement from adjacent nodes. The significance of these findings is discussed.

Cerebrospinal fluid rhinorrhea and unilateral nasal polyposis: a case report.

We report a case of cerebrospinal fluid (CSF) rhinorrhea and unilateral polyposis in a 53-year-old woman. The clinical features, tomograms, and CT scan with Metrizamide infusion are examined. The analysis of this case evidences that: 1) A CSF can occur also after a long time (3 years) following a head injury; 2) CT cisternography with Metrizamide can demonstrate a leakage, but not always the fluid egress from the intracranial cavity; and 3) A CSF rhinorrhea may be the primary cause and not an occasional association or complication of a reactive phlogistic nasal disease.

Prostaglandins in squamous cell carcinoma of the larynx: tumor and peritumor synthesis.

Prostaglandin (PG) E2, 6ketoPGF1 alpha and Thromboxane B2 (TxB2) production by the tumor, peritumor and control tissue were investigated in specimens from patients (n = 11) with squamous cell carcinoma of the larynx, in relation to the extension and infiltration of the neoplasm and to the presence of inflammation, fibrosis and necrosis. In all specimens detectable amounts of 6ketoPGF1+ and TxB2 were found, but the predominant metabolite was PGE2. No differences in the levels of TxB2 and 6ketoPGF1 alpha were observed, but the only patient with lymphnodal involvement showed the lowest levels of 6ketoPGF1 alpha both in tumor and peritumor tissue. Higher amounts (p less than 0.05) of PGE2 were synthesized by peritumor tissues in comparison to control mucosa and tumor tissue independently of the occurrence of reactive infiltration. PGs synthesis did not correlate with inflammation, fibrosis, necrosis or staging of the neoplasm. However the two cases in stage T4 showed PGE2 generation at the highest levels both in neoplastic and perineoplastic tissue. These findings indicate that in squamous cell carcinoma of the larynx an increased production of PGE2 occurs, stemming not only from inflammatory cells but at least in part from neoplastic cells. This suggests that the study of arachidonic acid metabolism may contribute to characterization of the primary cancer and lead to better understanding of the mechanisms of tumor growth and diffusion.

Pharmacokinetics of cis-diamminedichloroplatinum(II) after administration in hypertonic saline.

Nephrotoxicity, the dose-limiting toxicity of cis-diamminedichloroplatinum(II) (CDDP), is ameliorated when administered in hypertonic saline with normal saline hydration. To determine whether the diminished nephrotoxicity is associated with alteration of the pharmacokinetics of CDDP, we examined the pharmacokinetics of free and total platinum, platinum renal excretion, and urine electrolytes in patients given CDDP in hypertonic saline and in patients given CDDP in a conventional manner. The pharmacokinetics of free and total platinum for equal doses of CDDP were similar regardless of the vehicle of administration and the method of hydration. CDDP given in a vehicle of high chloride concentration with normal saline hydration resulted in a statistically significant increase in both urine volume and chloruresis compared to the conventional regimen. The decreased nephrotoxicity associated with administration of CDDP in hypertonic saline with saline diuresis may be related to increased chloruresis, urinary volume, or a combination of both, but did not appear to be related to an alteration in the pharmacokinetics.