Differentiation of squamous cell carcinoma and inverted papilloma using non-invasive MR perfusion imaging.

OBJECTIVES: To investigate the diagnostic value of tumour blood flow (TBF) obtained with pseudocontinuous arterial spin labelling for the differentiation of squamous cell carcinoma (SCC) and inverted papilloma (IP) in the nasal or sinonasal cavity. METHODS: We retrospectively analysed the cases of 33 patients with SCC and 8 patients with IP in the nasal or sinonasal cavity. Pseudocontinuous arterial spin labelling scanning was performed for all patients using a 3.0-T MR unit. Quantitative TBF values were measured by two neuroradiologists by respectively delineating the whole-tumour regions of interest, and the mean of them was determined as TBF value in each patient. Additionally, the presence of imaging findings of convoluted cerebriform pattern (CCP) on MR T2 weighted images was determined in all patients. As a subgroup analysis, patients with IP were divided into aggressive and non-aggressive IPs depending on their progression range. First, an intraclass correlation coefficient (ICC) of TBF values between two neuroradiologists was determined. Next, a statistical comparison of the TBF value by a Mann-Whitney U test between the patients with SCC and IP was performed. Additionally, the comparison by an ANOVA with a post hoc test of Tukey's method among the SCC, non-aggressive IP and aggressive IP groups was also performed. If significance was observed, the diagnostic accuracy to differentiate SCCs from IPs was calculated. Diagnostic accuracy by CCP findings alone and by the combination of CCP findings and TBF were also assessed. RESULTS: The ICC of TBF values between two neuroradiologists was 0.82. The mean TBF values in the patients with SCC, all patients with IP, those with aggressive IP and those with non-aggressive IP were 141.2 ± 33.1, 77.8 ± 31.5, 109.4 ± 16.7 and 58.8 ± 19.9 ml 100 g⁻¹ min⁻¹, respectively. A significant difference was observed between SCC and IP (p < 0.001), SCC and non-aggressive IP (p < 0.01) and non-aggressive IP and aggressive IP (p < 0.01). The diagnostic accuracy values obtained with receiver operating characteristic curve analysis for the differentiation of SCC from IP and for SCC from non-aggressive IP were 0.90 and 0.92, respectively. The diagnostic accuracy was elevated (0.95 from 0.88) by adding the TBF value to CCP findings. CONCLUSIONS: The pseudocontinuous arterial spin labelling technique can be a useful non-invasive diagnostic tool to differentiate SCC from IP in nasal or sinonasal cavity.

The role of tissue factor pathway inhibitor-2 in malignant transformation of sinonasal inverted papilloma.

The aim was to evaluate the potential role of tissue factor pathway inhibitor-2 (TFPI-2) in the process of malignant transformation of sinonasal inverted papilloma (SIP). We evaluated the expression of TFPI-2 in 23 SIP and 8 SIP with squamous cell carcinoma (IPcSCC), compared to 9 normal sinonasal mucosa by means of Western blot and immunohistochemistry staining. In addition, angiogenesis, vascular endothelial growth factor (VEGF) expression and microvessel density marked by CD105 staining were assessed. Correlation of TFPI-2 expression and angiogenesis in the process of malignant transformation of SIP was investigated. Western blot results demonstrated that the protein level of TFPI-2 in IPcSCC was significantly lower than that in the control group (P < 0.01). In addition, significant difference in TFPI-2 protein expression between SIP and IPcSCC was detected (P < 0.01). Higher number of microvessel per unit area (MVNA) was observed in IPcSCC compared to SIP (P < 0.01). Correlational analysis indicated positive correlation of VEGF and MVNA (r = 0.735), inverse correlation of TFPI-2 and MVNA (r = -0.318). However, no significant correlation between TFPI-2 and VEGF was detected. We conclude that TFPI-2 might be a regulatory molecule in the malignant potential of SIP. Down regulation of TFPI-2 is associated with increased MVNA in IPcSCC, which may be involved in the process of malignant transformation of SIP.

Significant improvement in superselective intra-arterial chemotherapy for advanced paranasal sinus cancer by using indocyanine green fluorescence.

Recent advances in indocyanine green (ICG) fluorescence imaging have enabled the visualization of the blood supply to tissues. For advanced head and neck cancer, intra-arterial chemotherapy has been applied for improving the prognosis and organ preservation. To identify the tumor-feeding artery, CT angiography has been shown to be useful. However, the presence of dental metals sometimes disturbs the precise evaluation of paranasal sinus cancer patients by CT angiography. The objectives of the study were to assess the feasibility of the ICG fluorescence technique during intra-arterial chemotherapy for advanced maxillary cancer. Thirty-six patients with paranasal sinus cancer who were treated by intra-arterial chemotherapy were included. Conventional CT angiography followed by 5 mg of ICG injection was performed to confirm the areas in which the drug had dispersed. Intra-arterial chemotherapy was administered at 150 mg/m(2) of CDDP four times weekly. Additional information about the arteries feeding the tumors provided by ICG was evaluated. Out of 36 cases, in 17 (47%) the blood supply to the cancer was clearly detected by CT angiography. By adding the infrared ICG evaluation, the blood supply to the tumor was confirmed easily in all cases without radiation exposure. The information obtained from fluorescence imaging was helpful for making decisions concerning the administration of chemo-agents for paranasal sinus cancers in cases involving dental metal, or skin invasion. ICG fluorescence imaging combined with intra-arterial chemotherapy compensated for the deficiencies of CT angiography for paranasal sinus cancer. ICG fluorescence provided us clearer and more useful information about the feeders to cancers.

[Correlation of VEGF expression with microvessel and microlymphatic density in sinonasal squamous cell carcinoma].

OBJECTIVE: To study the expression of VEGF in sinonasal squamous cell carcinoma and its correlations with microvessel density (MVD), microlymphatic vessel density (MLVD). METHOD: The expression of VEGF, MVD and MLVD in 41 cases of sinonasal squamous cell carcinoma were detected by immunohistochemical technique. RESULT: In the sinonasal squamous cell carcinoma, the positive rate of VEGF was 82.9% (34/41). The over expression of VEGF was related with tumor invasion, histological grading and lymphatic metastasis (P < 0.05). The MVD of cases with positive VEGF expression was significantly higher than those without VEGF expression (P < 0.05), but was not statistical difference in MLVD (P > 0.05). CONCLUSION: VEGF may participate in the metastasis of sinonasal squamous cell carcinoma through promoting vascularization in the tumors, but not promoting MLVD.

Lack of correlation between microvascular density and pathological features and outcomes in sinonasal and oral mucosal melanomas.

Unlike its cutaneous counterpart, prognostic markers for primary mucosal malignant melanoma have not been well elucidated. It has been recently demonstrated that microvascular density (MVD) in cutaneous malignant melanoma has a significant negative correlation with survival; however, this has not been well-studied in mucosal malignant melanoma of the head and neck. This study explores the potential association between MVD, various histological parameters, and the outcome of a series of sinonasal and oral mucosal melanomas. Nineteen such cases were immunostained with CD31 and the MVD was calculated by using Bioquant Image Analysis Software (R and M Biometrics, Nashville, TN). These cases included 16 sinonasal and 3 oral cavity tumors. The 1, 2, 3, 4 and 5 years overall survival rates were 75, 57, 61, 46 and 46%, respectively. The MVD of the tumors ranged from 25.7 to 732 vessels/mm(2) (mean 142.8 vessels/mm(2); median 84.7 vessels/mm(2)). There was no significant correlation between the MVD and the different clinicopathological features seen within the tumors. There was also no correlation between the MVD and relapse free and overall survival. The results of this study suggest that MVD does not correlate with outcome in mucosal melanoma of the head and neck as seen in cutaneous melanomas. Further larger studies are needed to identify predictive and prognostic markers in such melanomas.

[Cluster analysis in micrangium detection in malignant nasal and paranasal sinus tumor].

OBJECTIVE: To study the application of cluster analysis in micrangium detection in malignant nasal and paranasal sinus tumor. METHODS: Microvessel density (MVD) counting and cluster analysis were used to detect the micrangium in patients with malignant nasal and paranasal sinus tumor to assess the association between the malignancy and MVD. RESULTS: According to cluster analysis, the MVD counting could be clustered into two groups, and the MVD showed significant differences between the tumor tissues, adjacent normal tissue and the control group (P<0.01), a result consistent with that by analysis of variance of the MVD. CONCLUSION: Cluster analysis can be used in clustering of MVD counting in malignant nasal and paranasal sinus tumor to simplify MVD counting, and offers an important analytic method for micrangium analysis in tumors.

Clinicopathological implications of tumour-associated macrophages and vascularization in sinonasal melanoma.

This study investigated tumour-associated macrophages (TAMs) and their effects on tumour vascularization in sinonasal melanoma (SNM). Data on 45 patients with SNM undergoing surgery were reviewed retrospectively. Tumour sections were analysed immunohistochemically for TAMs, microvessels, lymph vessels, and vasculogenic mimicry in both intra- and peritumoural areas. The density of intratumoural TAMs was associated with tumour thickness and with overall survival in SNM stages I and II but there were no correlations between micro- or lymph vessel density and TAM infiltration. Greater TAM infiltration was observed in tumour tissues with vasculogenic mimicry although this was not statistically significant. These data suggest that high intratumoural TAM infiltration is associated with tumour aggressiveness and a poor prognosis for SNM, and that activation of macrophages can be polarized by different micro-environments. TAMs could be potential prognostic indicators for patients with SNM.

Clinical and biological prognostic factors in 179 cases with sinonasal carcinoma treated in the Italian Piedmont region.

OBJECTIVES: In spite of aggressive surgery and high-dose radiotherapy, the long-term survival of patients with sinonasal cancer remains disappointing. In this paper, we report data from 179 consecutive cases treated in the Italian Piedmont region between 1996 and 2000 according to a fixed protocol. METHODS: Clinical and pathological data and the following biological parameters were analyzed: microvessel density and growth fraction by CD31 and Ki-67 positivity, respectively, and immunohistochemical expression of vascular endothelial growth factor (VEGF). RESULTS: The median follow-up period was 75 months (range 45-108 months). Median overall survival was 26 months; 2- and 5-year overall survival rates were 52 and 36%, respectively. Patients with T1-T2 adenocarcinoma and squamous cell cancers (SCC) had better median survival than those with other lesions (p < 0.05). Patients treated with surgery with or without radiotherapy had better survival (p < 0.01), while chemotherapy had a marginally favorable effect (p = 0.09). The type of surgery and radiotherapy dose had no impact on survival; in contrast, there was a strong association between Ki-67 expression and microvessel density and overall survival (p < 0.05 and p = 0.039, respectively), while VEGF-C was a prognostic factor in SCC patients only (p < 0.05). CONCLUSIONS: In sinonasal cancer, tumor stage and histology have a clear impact on survival; surgery with or without radiotherapy represents the main choice of treatment for such tumors. The efficacy of neoadjuvant and concomitant chemoradiotherapy needs to be further investigated. The proliferative index and angiogenesis show a major role in the natural history of this cancer.

[Endoscopic surgical treatment of vascular tumors of the paranasal sinuses and base of the skull].

Fourteen endonasal endoscopic operations for vascular tumors of the paranasal sinuses, mainly of stage II-III, were performed in 1997-2006. In one case intraoperative navigation was used. Preoperative angiography was made in 4 patients with a definite diagnosis of hemangioma. Out of them, in three cases preoperative embolisation of the afferent vessel was conducted; apparent vascular bed in tumor stroma was not found. Follow-up from 1 to 8 years registered no further growth of the tumor in patients operated endoscopically.

Meningioma of the paranasal sinus: a case report.

Extracranial meningioma of the paranasal sinus is a very rare condition of unclear etiology. Surgical excision is currently the only curative treatment but sometimes entails difficulties because of the complicated anatomic loci of the tumor. For the case reported here, we used a navigation system in endoscopic surgery for an extracranial meningioma of the paranasal sinus and were able to remove the tumor without complications by a transnasal approach alone. This is the first report of the use of such a system with endoscopic surgery for this condition. We discuss the clinical presentation, diagnosis, and treatment of this case as well as present a review of the literature.

Endoscopic sinus surgery for the treatment of vascular tumors.

BACKGROUND: This study points out the effectiveness of the endoscopic approach for the treatment of vascular lesions such as angiofibroma, hemangioma, and hemangiopericytoma involving the nose and paranasal sinuses. METHODS: We performed a retrospective study at an academic tertiary referral center. Thirteen patients, diagnosed with vascular tumors of the nose and paranasal sinuses were treated endoscopically between February 1996 and July 2003. All patients underwent endonasal endoscopic surgery. Preoperative angiography with embolization was performed in all but two cases. RESULTS: The follow-up of this series varied from 6 to 75 months (mean, 23 months); only one recurrence (8%) was observed in the juvenile angiofibroma group encountered 20 months postoperatively. This recurrence was again treated endoscopically. The average intraoperative blood loss for the removal of the juvenile angiofibroma group was 300 mL and it was 100 mL for the other vascular tumors. CONCLUSION: Endoscopic treatment alone is an effective approach for the removal of selected cases of vascular tumors. Even in the presence of a lesion with limited intracranial extension, the tumor still may be amenable to an endoscopic approach alone. On the contrary, this is not true if the intracranial extension receives feeding vessels from the internal carotid arterial system.

Prognostic significance of microvessel density and vascular endothelial growth factor expression in sinonasal carcinomas.

The prognostic significance of microvessel density and proliferative activity of the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and immunohistochemical expression of vascular endothelial growth factor (VEGF) was retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical specimens and 25 biopsies). The most represented histologic types were intestinal-type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC) in 34 (32.4%), mucinous adenocarcinoma (mainly made up of signet-ring cell patterns) in 15 (14.3%), and adenoid cystic carcinoma in 7 (6.7%). Microvessel density values (in vessels per square millimeter), VEGF, and Ki-67 were not dependent on histologic type but were rather correlated to the histologic grading in SCC. Clinical data were available for 92 (87.6%) of 105 patients, with minimum follow-up of 48 months. Most of the patients (81.5%) were at an advanced stage (T3-T4) at diagnosis. The values of all markers were correlated to tumor stage (P = .03). Multivariate analysis showed that both microvessel density and proliferative activity of the neoplastic cells were independent prognostic parameters (mortality hazard ratio, 1.33 and 1.60, respectively). Although VEGF expression was not correlated to prognosis on the whole series (P = .06), it was a powerful prognostic marker when the analysis was restricted to the group of SCCs (hazard ratio, 3.02; 90% confidence interval, 1.58-5.80). These results show that tumor neoangiogenesis, expressed by microvessel density, together with proliferative activity, is a pathologic marker with a strong prognostic impact in sinonasal carcinomas. Therefore, it may be a useful tool in this field so as to carry out therapeutic protocol planning, which may be further enhanced by the adoption of the more recent antiangiogenic molecules.

Carotid artery resection: preoperative temporary occlusion is not always an accurate predictor of collateral blood flow.

CONCLUSION: The morbidity predicted by means of preoperative PET studies does not always correlate with the morbidity experienced after permanent carotid artery occlusion. A pre-resection extracranial-intracranial bypass may be necessary to reduce the risk of neurologic morbidity, in particular when carotid artery resection is planned for tumors involving the skull base. OBJECTIVES: Carotid artery resection is generally considered the only curative treatment for patients with advanced head and neck carcinoma involving the carotid artery. PET can be used during temporary occlusion of the internal carotid artery to assess the safety of the procedure. The aims of this paper were to clarify the risk of carotid artery resection and the benefit of extracranial-intracranial bypass. MATERIAL AND METHODS: Twelve patients diagnosed with head and neck cancer adherent to the carotid artery and in proximity to the skull base who had shown good hemispheric collateral blood flow by means of PET underwent carotid artery resection without preoperative bypass. RESULTS: Of the 12 patients who underwent carotid artery resection without reconstruction, 10 suffered no serious neurologic complications; however, 2 suffered cerebral infarctions intraoperatively.

Infarcted angiomatous nasal polyps.

Angiomatous nasal polyps are a rarely reported subtype of inflammatory sinonasal polyps that are characterized by extensive vascular proliferation and ectasia. Compromise of their vascular supply may occasionally lead to infarction, resulting in clinical, radiological and pathological features that simulate a neoplastic process. In the present paper, the salient characteristics of this unusual entity are described. The clinical, radiological and pathological features of two patients with infarcted angiomatous nasal polyps are presented. Grossly, the polyps had an unusual inhomogenous appearance and texture and were associated with a foul odor. CT findings included bony expansion and destruction. MRI findings included markedly inhomogenous contrast enhancement on T1-weighted images. Histopathologically, both cases showed abundant vascular ectasia, with widespread intraluminal thrombosis and necrosis. Recanalization and reparative changes were also present. Angiomatous nasal polyps are poorly documented in the literature. Although entirely benign, they may simulate neoplastic processes, thus awareness of their existence is of considerable importance.

Metastasis of renal cell cancer to the ethmoid sinus.

The origin of metastatic tumors in the nasal or paranasal sinuses is often renal cancer, and metastasis to the nasal or paranasal sinuses sometimes takes a long time after nephrectomy. The present paper deals with one patient with metastasis of renal cancer to the ethmoid sinus 2 years after nephrectomy. Even though many metastatic tumors originating from renal cancer develop in multiples, most metastatic tumors in the nasal or paranasal sinuses are single and treated surgically. However, even if multiple tumors are found in the nasal and paranasal region and other organs, surgery will be effective in preventing epistaxis and subsequent anemia. Also, when removing a tumor it will be effective to identify the feeding arteries of the tumor, perform embolization therapy, and clip the necessary arteries.

[Ectopic meningioma of the ethmoid sinus: case report and a review of the literature].

A rare case of ectopic meningioma of the ethmoid sinus is reported. A 57 year-old male patient was admitted with complaints of anosmia and headache. Computed tomography revealed a relatively high-density mass in the bilateral ethmoid and sphenoid sinuses. The mass was markedly enhanced after intravenous administration of contrast medium. The cerebral angiography showed tumor stains fed by bilateral internal and external carotid arteries with right side dominance. The tumor in the ethmoidal sinus was removed by otolaryngologists at first and then the tumor in the sphenoid sinus was removed using sublabial transseptal sphenotomy. The histological examination resulted in a diagnosis of transitional meningioma with psammoma bodies. The tumor in this case is suspected to have originated from heterotopic meningocytes or meningocytes accompanying the perineural sheath of the olfactory nerve.

Angiography in the diagnosis and management of extracranial vascular lesions of the head and neck.

The angiographic features of various lesions of the head and neck are presented. Angiographically, cavernous hemangiomas display large venous lakes with calcified phleboliths. Arteriovenous malformations reveal massive tumor stain with well delineated feeding vessels from multiple systems. Chemodectomas and juvenile nasopharyngeal angiofibromas are clearly vascular with homogenous tumor staining in the capillary phase. Angiography of cavernous hemangioma, AVM, chemodectoma, and angiofibroma is diagnostic and may preclude the need for tissue biopsy. Angiographically neurilemmomas are less vascular with non-homogenous tumor stain. Carcinomas are typically avascular. The use and benefits of arterial embolization in the management of these lesions is presented.