Review of histologic and immunohistochemical features of spindle cell carcinomas (carcinosarcomas) of the larynx.

BACKGROUND: Laryngeal carcinosarcomas pose a significant diagnostic challenge to the pathologist; differential diagnosis needs histochemical and immunohistochemical investigations. MATERIALS AND METHODS: A retrospective review of charts of the pathology database was performed by a search for carcinosarcoma cases. Immunohistochemistry was performed on the representative paraffin blocks in all cases. RESULTS: This study included a total of 5 cases of carcinosarcomas of the larynx. The sarcomatoid component of the tumor was arranged in various patterns mimicking mesenchymal malignancies. Tumor cells were seen arranged in fascicles (a patient), in a storiform (3 patients), or in a solid (a case) pattern. The epithelial markers EMA and AE1/AE3 were positive in all 5 patients, as well as vimentin and CK34betaE12. DISCUSSION: Immunohistochemical studies of epithelial and mesenchymal markers (such as AE1/AE3, epithelial membrane antigens, vimentin, desmin, and S-100) are fundamental to diagnose the tumor, although they may widely vary.

The management of an orbital diffuse large B-cell lymphoma.

BACKGROUND: The orbit represents a rare site of presentation of non-Hodgkin lymphoma. The diagnosis and management of orbital lymphomas may be challenging because these neoplasms present few specific features. METHODS: A 69-year-old woman presented with painless swelling of the left lower eyelid of 5 years' duration. Magnetic resonance imaging and incisional biopsy were necessary to establish a diagnosis of orbital diffuse large B-cell lymphoma. Staging was completed, thanks to a computed tomographic study of the chest and abdomen. RESULTS: The patient underwent systemic chemotherapy with 1 regimen (doxorubicin, vincristine, prednisone, 6-mercaptopurine, and methotrexate), followed by 1 R-COMP-14 regimen (rituximab, cyclophosphamide, nonpegylated liposome-encapsulated doxorubicin, vincristine, and prednisone). Complete resolution of the disease was obtained. CONCLUSIONS: Although not typically performed by the head and neck surgeon, an understanding of the staging process is crucial for multidisciplinary management of orbital lymphomas.

Towards the eradication of HPV infection through universal specific vaccination.

BACKGROUND: The Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm including condylomas and penile, anal, vulvar, vaginal, and oro-pharyngeal cancers. Men play a key role in the paradigm of HPV infection: both as patients and as part of the mechanisms of transmission. Data show they are affected almost as often as women. Moreover, no screening procedures for HPV-related disease prevention are applied in men, who fail to undergo routine medical testing by any medical specialist at all. They also do not benefit from government prevention strategies. DISCUSSION: A panel of experts convened to focus on scientific, medical, and economic studies, and on the achievements from health organizations' intervention programs on the matter. One of the goals was to discuss on the critical issues emerging from the ongoing global implementation of HPV vaccination. A second goal was to identify contributions which could overcome the barriers that impede or delay effective vaccination programs whose purpose is to eradicate the HPV infection both in women and men. SUMMARY: The reviewed studies on the natural history of HPV infection and related diseases in women and men, the increasing experience of HPV vaccination in women, the analysis of clinical effectiveness vs economic efficacy of HPV vaccination, are even more supportive of the economic sustainability of vaccination programs both in women and men. Those achievements address increasing and needed attention to the issue of social equity in healthcare for both genders.

Prevalence and characteristics of HPV infection in oropharyngeal cancer.

BACKGROUND: The purpose of this prospective study was to analyze the human papillomavirus (HPV) infection status and its impact on the outcome in a consecutive series of patients affected by oropharyngeal cancer. METHODS: The specimens of consecutive subjects surgically treated for oropharyngeal squamous cell carcinoma were obtained. Samples were collected by broom-type cell sampling devices and they underwent the Roche Linear Array HPV Genotyping Test to identify the presence of HPV types. RESULTS: In all, 52 patients were enrolled. The presence of HPV was detected in 13 samples, with HPV type 16 as the most frequently encountered type. Statistically significant associations were found between HPV-positive patients and a higher tumor grading (P < 0.05), and between HPV-positive patients and a higher number of negative prognostic factors (P < 0.05). CONCLUSIONS: A subset of oropharyngeal squamous cell carcinomas with a higher tumor grading is strongly linked to HPV16 infection.

Diagnostic classification of persistent rhinitis and its relationship to exhaled nitric oxide and asthma: a clinical study of a consecutive series of patients.

BACKGROUND: Rhinitis and asthma represent the manifestation of one syndrome. Our hypothesis is that in patients with symptoms of persistent rhinitis, lower airway inflammation, lower respiratory symptoms, and lung function abnormalities compatible with asthma are more frequently associated with the diagnosis of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) than with nonallergic rhinitis (NAR). METHODS: One hundred eight of 590 consecutive patients referred in 1 year for rhinitis were enrolled on the basis of nasal symptoms lasting > 4 weeks. Asthma was diagnosed on the basis of symptoms and a positive bronchodilation testing result and/or methacholine hyperresponsiveness. Exhaled nitric oxide (Feno) was measured with the single exhalation method at 50 mL/s. RESULTS: AR was diagnosed in 39%, NAR in 21%, and CRS in 40%. The prevalence of asthma was significantly higher in AR patients (33%) and CRS patients (42%) than in NAR patients (8.7%) [p = 0.036 and p = 0.005, respectively]. Feno was significantly higher in patients with AR and CRS compared to patients with NAR (44.3 parts per billion [ppb]; 95% confidence interval [CI], 34 to 54 ppb; and 53 ppb; 95% CI, 42 to 64 ppb; vs 22 ppb; 95% CI, 18 to 27 ppb; p = 0.002 and p = 0.001, respectively). Patients with asthma had Feno values significantly higher than patients without asthma (64 ppb; 95% CI, 51 to 77 ppb; vs 33.3 ppb; 95% CI, 28 to 39 ppb; p < 0.001). CONCLUSIONS: The diagnostic classification of persistent rhinitis helps to predict lower airway inflammation (increased Feno) and prevalence of asthma: AR and CRS are associated with higher mean Feno values and higher prevalence of asthma than NAR.

Exhaled nitric oxide as a diagnostic test for asthma in rhinitic patients with asthmatic symptoms.

BACKGROUND: Rhinitis is a major risk factor for asthma, so that evaluation of the lower airways is recommended in patients with rhinitis. Exhaled nitric oxide (FE(NO)) is considered a marker of airway inflammation and it has been found to be useful for the screening of patients with suspected diagnosis of asthma. Our aim was to assess the validity and accuracy of FE(NO) to identify patients with asthma in 48 non-smoking patients with persistent rhinitis and asthma-like symptoms. METHODS: Asthma was diagnosed on the basis of 12% improvement in FEV1 after salbutamol or a methocholine PD(20)FEV1<800 microg. Prior to lung function FE(NO) was measured with the single exhalation method at 50 ml/s. RESULTS: The geometric mean (95% confidence interval) FE(NO) was significantly higher in the 18/48 asthmatics than in the non-asthmatic patients (60 ppb, CI 95%: 50-89, versus 30 ppb, CI 95%: 28-45, P=0.001). Receiver operating characteristic (ROC) curve for the diagnosis of asthma indicated that FE(NO) is an acceptable discriminator between patients with and without asthma (area under the ROC curve=0.78). None of the asthmatic patients had FE(NO) values<25 ppb and all the patients with FE(NO)>100 ppb (n=5) were asthmatics. The sensitivity and specificity of FE(NO) for detecting asthma, using 36 ppb as cut-off point, were 78% and 60% and the positive and negative predictive values were 54% and 82%, respectively. CONCLUSIONS: Measuring FE(NO) may be useful for the screening of rhinitic patients with asthma-like symptoms.

Determinants of exhaled nitric oxide in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) has been reported to be associated with increased values of exhaled nitric oxide (ENO), which could not be entirely explained by the association between CRS and asthma. The aim of this study was to investigate the variables associated with increased ENO in patients with CRS. METHODS: This was a prospective cross-sectional descriptive study of 93 consecutive patients with CRS. The effect on ENO of age, gender, atopy, asthma, respiratory symptoms without bronchial hyperresponsiveness (BHR), and nasal polyps was evaluated by multiple regression analysis. RESULTS: Nasal polyps (P = .01), asthma (P < .001), and respiratory symptoms without BHR (P = .01) were the only independent variables associated with increased ENO. The prevalence of asthma was significantly higher in subjects with nasal polyps (61% vs 29.4%), P = .005, whereas the prevalence of respiratory symptoms without BHR was higher in those without nasal polyps (44.1% vs 15.3%, P = .003). Respiratory symptoms without BHR were associated with significantly higher ENO and prevalence of sputum eosinophilia (eosinophils > 3%) in patients with nasal polyps compared with those without nasal polyps (68.2 vs 24.0 ppb, P = .001; 60% vs 8.3%, P = .03, respectively). CONCLUSIONS: The presence of nasal polyps in patients with CRS was associated with increased asthma prevalence as well as increased ENO levels. Respiratory symptoms without BHR were associated with eosinophilic airway inflammation and increased ENO only in patients with nasal polyps. These findings suggest important clinical and biologic differences between the two types of CRS, with and without nasal polyps.

Nasal nitric oxide concentration in suspected chronic rhinosinusitis.

BACKGROUND: The role that nasal nitric oxide (nNO) plays in sinonasal diseases is increasingly appreciated. OBJECTIVE: To test the diagnostic value of measuring nNO levels in a symptomatic population undergoing evaluation for potential chronic rhinosinusitis (CRS). METHODS: Of the patients referred to an outpatient allergy clinic for persistent nasal symptoms, those reporting nasal blockage plus 1 or more additional symptoms (discolored discharge, anterior or postnasal drip, facial pain or pressure, and reduction or loss of smell) were categorized as having CRS according to sinus computed tomography scores, with (CRSwNP) and without (CRSsNP) nasal polyps on the basis of endoscopic signs. All the included patients underwent nNO measurement and skin prick tests for common inhalant allergens. Healthy individuals served as controls for nNO measurement. RESULTS: Levels of nNO were significantly lower in patients with CRSwNP (median, 340 ppb; 25th-75th percentile, 145-390 ppb) compared with patients with CRSsNP (762 ppb; 620-1,013 ppb), patients without CRS (917 ppb; 647-1,159 ppb), and controls (843 ppb; 762-962 ppb) (P < .001). Low values of nNO separated very well patients with CRSwNP, and the nNO cutoff value of less than 442 ppb was associated with the best combination of specificity (91%) and sensitivity (87%), resulting in a negative predictive value of 91% and a positive predictive value of 87%. A significant inverse relationship was observed between nNO level and sinus computed tomography score (r2 = -0.39, P < .001). CONCLUSION: Testing for nNO is highly predictive of CRSwNP in a selected population of patients with symptoms suggestive of CRS.

Improved survival with perilymphatic interleukin 2 in patients with resectable squamous cell carcinoma of the oral cavity and oropharynx.

BACKGROUND: The current randomized, multicenter, Phase III trial was conducted to determine whether the disease free interval and overall survival of patients with T2-T4,N0-N3,M0 squamous cell carcinoma (SCC) of the oral cavity or oropharynx could be extended through the combination of surgery (and radiotherapy, if required) with perilymphatic recombinant IL-2 (rIL-2). METHODS: Patients with a resectable T2-T4,N0-N3,M0 SCC of the oral cavity and oropharynx were assigned randomly to receive surgery and radiotherapy or to receive IL-2, surgery, and radiotherapy. Five thousand units of rIL-2 were injected around the ipsilateral cervical lymph node chain daily for 10 days before surgery. After surgery, contralateral 5-day rIL-2 courses were administered monthly for 1 year. The differences in disease free and overall survival between the two groups of patients were evaluated statistically. RESULTS: Two hundred two patients finished the study. No significant complications related to rIL-2 were encountered, and surgery and radiotherapy were not hampered by its prior administration. Multivariate analysis conducted to determine the extent to which survival was influenced by rIL-2 and the other variables showed that rIL-2 significantly lengthened disease free survival (P < 0.01) and that this resulted in longer overall survival (P < 0.03). CONCLUSIONS: The data emerging from this trial indicate that perilymphatic administration of low, nontoxic doses of rIL-2 is a simple and manageable way to delay recurrences of SCC.