Diagnostic value of serum squamous cell carcinoma antigen and cytokeratin fragment antigen 21-1 for sinonasal inverted papilloma: an exploratory study.

BACKGROUND: Serum tumor markers have not yet been developed for the clinical diagnosis and treatment of sinonasal inverted papilloma (SNIP), one of the most significant sinonasal tumors. Therefore, this study aimed to determine the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) for SNIP. METHODS: Clinical data were obtained from 101, 56, and 116 patients with SNIP, sinonasal squamous cell carcinoma (SNSCC), and unilateral chronic rhinosinusitis (CRS), respectively. Preoperative serum SCCA and CYFRA 21-1 levels were compared, and logistic regression analyses were performed to screen serum tumor markers, which may be used to diagnose SNIP. Diagnostic cut-off values were determined using receiver operating characteristic (ROC) curves, and their diagnostic power was verified. RESULTS: Serum SCCA and CYFRA 21-1 differentiated SNIP from CRS with the cut-off values of 1.97 ng/mL and 2.64 ng/mL and the areas under the ROC curves (AUC) of 0.895 and 0.766, respectively, and the AUC of the combination of the two markers was 0.909. CYFRA 21-1 differentiated SNIP with malignant transformation from that without malignant transformation with a cut-off value of 3.51 ng/mL and an AUC of 0.938. CYFRA 21-1 distinguished SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/mL and an AUC of 0.767. CONCLUSIONS: This study provides novel potential diagnostic tools for SNIP by demonstrating the use of serum SCCA and CYFRA 21-1 in the diagnosis of SNIP.

Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside.

PURPOSE OF REVIEW: Sinonasal cancers are a heterogenous group of rare cancers for which histopathological diagnosis can be very challenging and treatment options are limited for advanced disease in particular. Here, we review the candidacy of novel diagnostic and prognostic biomarkers, and therapeutic targets for sinonasal cancers. RECENT FINDINGS: Molecular multidimensional analyses of sinonasal cancers have been lagging behind other major cancers, but there are numerous publications describing the discovery of novel candidate biomarkers, e.g. the methylation classifier, originally developed for brain cancers, and gene expression panels for the prediction of response to induction chemotherapy in sinonasal undifferentiated carcinoma. The most promising biomarkers are summarized and discussed further with regard to their clinical applicability and future potential. Many of the described novel biomarkers for sinonasal cancers will eventually overcome the pitfalls associated with the frequently non-specific immunohistological tests. With comprehensive, multidimensional molecular testing of these tumours in collaborative consortia projects, our better understanding of the molecular mechanisms of sinonasal cancers and their carcinogenesis will determine the most useful diagnostic and prognostic biomarkers, allow stringent multi-institutional validation and guide trials on targeted therapies.

Attachment-oriented endoscopic surgical management for inverted papillomas in the nasal cavity and paranasal sinuses.

OBJECTIVE: The treatment of all forms of sinonasal inverted papilloma (IP) is a complete, wide, local resection. The main surgical purpose is to remove all diseased mucosa and mucoperiosteum, together with a cuff of normal-looking mucosa at the attachment site, followed by drilling and/or coagulation. Our aim is to present our experiences in endoscopic surgical management of IP by using attachment-oriented excision. METHODS: We present 20 cases of sinonasal IP. The data collected includes the histopathological diagnosis, staging, extension of the tumor, tumor attachment site, approach to surgery, serum squamous cell carcinoma antigen (SCCA) level, and recurrences. RESULTS: All patients underwent endoscopic surgery. A Caldwell-Luc operation was required in addition to the endoscopic surgery in one case. There was one case of recurrence (5%). After the additional operation, there was no recurrence. The tumor attachment sites vary, and the case of recurrence had a wide attachment site at the primary surgery. No major intra- or post-operative complications were observed. CONCLUSION: The present study shows that attachment-oriented excision for IP is useful for complete resection of IP. Surgeons should choose the surgical approach according to the location of the tumor attachment site rather than the Krouse staging system.

Varied presentation of sinonasal phosphaturic mesenchymal tumour: report of a case series with follow-up.

PURPOSE: Phosphaturic mesenchymal tumour (PMT) of the paranasal sinuses is a rare tumour that is associated with oncogenous osteomalacia causing predominant musculoskeletal symptoms. We present a series of eight patients diagnosed to have PMT of the paranasal sinuses with varied presentation and highlight the appropriate evaluation required to arrive at the diagnosis. METHODS: Retrospective review of eight patients diagnosed to have PMT-causing tumour-induced osteomalacia with follow-up data. RESULTS: Eight patients, 4 males and 4 females, aged 36-67 years (mean = 44 years) presented with vague musculoskeletal symptoms (6 patients) or epistaxis (3 patients). Six patients were found to have hypophosphatemia, phosphaturia and raised FGF-23 levels preoperatively. All eight patients were found to have a tumour in the nose and/ paranasal sinuses with one patient having intracranial extension. All patients were treated with endoscopic excision of these tumours which resulted in resolution of symptoms and normalisation of biochemical abnormalities. In addition, one patient required a craniofacial resection. Histopathological features were consistent with PMT mixed connective tissue variant. Two atypical patients were seen. The longest follow-up was for 5 years and there was no evidence of recurrence during the follow-up period in any patient. CONCLUSION: Diagnosis of PMT of the paranasal sinuses causing oncogenous osteomalacia requires a high index of suspicion when there are no ENT symptoms. Appropriate biochemical tests and histopathology lead to the correct diagnosis. Total endoscopic surgical excision leads to a good outcome.

The clinical value of serum squamous cell carcinoma antigens 1 and 2 in head and neck squamous cell carcinoma.

OBJECTIVE: The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC. METHODS: Serum samples for the analysis of SCCA1, SCCA2 and SCC antigen were taken from head and neck SCC patients before treatment. Serum SCC antigen was assayed with a solid phase immunoradiometric assay. The SCCA1 and SCCA2 protein level was determined by a sandwich ELISA. RESULTS: Fifty-two of 96 cases (54%) showed evaluated serum SCC antigen levels above the upper limit. The serum SCCA2 level was significantly higher in the head and neck SCC patients than in control group, whereas there were no significant differences in the serum SCCA1 level between head and neck SCC patients and control group. 72% of head and neck SCC patients demonstrated SCCA2 levels higher than 0.15, whereas 68% of the control subjects had SCCA2 levels less than 0.15. CONCLUSION: The serum SCCA2 levels were increased during the progression of cancer and might be a useful tool for the management of head and neck SCC.

Prognostic value of pretreatment peripheral blood markers in paranasal sinus cancer: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.

BACKGROUND: Pretreatment hematological markers have emerged as prognostic factors for several cancers. The purpose of this study was to present our investigation of the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting recurrence and mortality for patients with primary sinonasal cancers (SNCs). METHODS: We carried out a retrospective review of patients with SNC who had been treated using endoscopic approaches from 2002 to 2014 at a single institute. The endpoints analyzed were overall survival (OS) and disease-free survival (DFS). RESULTS: Of 365 patients treated, 215 fulfilled the inclusion criteria. Analysis of epithelial tumors (adenocarcinoma and carcinoma) and advanced-stage cancers (pT3-T4) showed shorter OS and DFS in those patients with higher NLR and PLR. Furthermore, the NLR and PLR were revealed as independent prognostic factors for DFS, with a reduced risk of recurrence in patients with NLR <2.6 (hazard ratio [HR], 0.39; p = .02) and PLR <156.9 (HR, 0.34; p = .001). CONCLUSION: High pretreatment NLR and PLR are associated with poor prognosis in patients affected by epithelial advanced-stage SNC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 730-736, 2017.

Postoperative value of serum squamous cell carcinoma antigen as a predictor of recurrence in sinonasal inverted papilloma.

OBJECTIVES: Sinonasal inverted papilloma (IP) has several unfavourable characteristics and therefore requires careful monitoring. The goal of this study was to identify whether serum squamous cell carcinoma antigen (SCCa) could predict IP recurrence. DESIGN: A retrospective cohort study. SETTING: Department of otolaryngology/head and neck surgery, Erasmus Medical Centre, Rotterdam, the Netherlands. PARTICIPANTS: One hundred and thirty patients with IP treated at our centre with SCCa measurements available were included. MAIN OUTCOME MEASUREMENTS: Follow-up of patients with IP since 2005, recurrence was defined as new disease within primary localisation at least 3 months after adequate surgical removal. We analysed the association between IP recurrence and serum SCCa values measured preoperatively, postoperatively and during follow-up. RESULTS: Preoperative SCCa values or values measured during follow-up were not associated with risk of recurrence. Postoperative SCCa was positively associated with the risk of recurrence (P < 0.001). Postoperative SCCa had a good discriminative ability for the identification of recurrence with an area under the curve of 80.9%. CONCLUSION: Postoperative SCCa is strongly associated with risk of recurrence. This might help the surgeon in the postoperative setting by identifying high-risk patients and planning follow-up strategy tailored to the individual patient.

Squamous cell carcinoma antigen as a marker of sinonasal inverted papilloma.

This prospective study aimed to evaluate the usefulness of squamous cell carcinoma antigen (SCCA) as a clinical marker of sinonasal inverted papilloma (IP). The potential benefit of SCCA in the diagnosis of unilateral nasal pathology and as a marker of hidden recurrence was evaluated as well. Blood samples from patients with sinonasal IP were examined to determine serum SCCA levels before surgery, the day after surgery, and every 6 months during follow-up. Preoperative and postoperative levels of SCCA were compared. Twenty consecutive patients with histologically confirmed IP were included in the study, conducted between 2000 and 2011. The mean age of the patients was 54.2 years (range 35-72). The mean serum SCCA level before surgery was 3.885 µg/l (range 0.7-7.6). A decrease of the SCCA level to 0.885 µg/l (range 0.1-1.9) was observed on the 1 day after a radical surgical procedure. A statistically significant difference between the preoperative and postoperative levels was observed (P < 0.001). Elevated levels of SCCA during long-term follow-up were observed in three patients. All of them had a recurrence of IP. We conclude that the serum level of SCCA is a useful clinical marker of the presence of sinonasal IP. The level of SCC antigen was significantly lower in patients after IP was completely removed. According to our results, SCCA level also appears to be useful for long-term follow-up (hidden recurrence diagnosis).

Germ cell tumors in atypical locations: experience of the TGM 95 SFCE trial.

The yolk sac tumor is one of the most common malignant germ cell tumors in young children and typically occurs in the gonads. We report 6 cases of children less than 30 months old with extragonadal atypical locations of yolk sac tumor. These rare diagnoses were established by raised serum α-fetoprotein levels and biopsies. These patients were treated according to the French TGM 95 trial. All the patients are alive disease-free after ≥2.5 years of follow-up. We want to highlight the importance of measuring the α-fetoprotein levels in very young children presenting with any midline tumor, even if the tumor is not located in the typical extragonadal sites such as the sacrococcyx, mediastinum, retroperitoneum, or vagina.

Elevated LDH and paranasal sinus involvement are risk factors for central nervous system involvement in patients with peripheral T-cell lymphoma.

BACKGROUND: The incidence and risk factors of central nervous system (CNS) involvement in peripheral T-cell lymphomas (PTCLs) are still unclear. PATIENTS AND METHODS: We analyzed 228 patients with PTCLs, excluding cases of extranodal natural killer/T-cell lymphoma and primary cutaneous T-cell lymphoma, by retrospectively collecting the clinical features and outcomes of the patients. RESULTS: Twenty events (8.77%, 20/228) of CNS involvement were observed during a median follow-up period of 13.9 months (range 0.03-159.43). Based on univariate analysis, elevated serum lactate dehydrogenase (LDH) level [P = 0.019, relative risk (RR) 5.904, 95% confidence interval (CI) 1.334-26.123] and involvement of the paranasal sinus (P = 0.032, RR 3.137, 95% CI 1.105-8.908) adversely affect CNS involvement. In multivariate analysis, both were independently poor prognostic factors for CNS relapse [elevated LDH level: P = 0.011, hazard ratio (HR) 6.716, 95% CI 1.548-29.131; involvement of the paranasal sinus: P = 0.008, HR 3.784, 95% CI 1.420-10.083]. The survival duration of patients with CNS involvement was significantly shorter than that of the patients without CNS involvement (P = 0.009), with median overall survival of 7.60 months (95% CI of 4.92-10.28) versus 27.43 months (95% CI of 0.00-57.38), respectively. CONCLUSIONS: Elevated LDH level and involvement of the paranasal sinus are two risk factors for CNS involvement in patients with PTCLs. Considering the poor prognoses after CNS relapse, prophylaxis should be considered with the presence of any risk factor.

A neuroendocrine tumour of the sphenoid sinus and nasopharynx: a case report.

It is rare for neuroendocrine tumours to originate in the sphenoid sinus and the nasopharynx. Neuroendocrine tumours can be classified into typical carcinoids, atypical carcinoids and small cell neuroendocrine carcinomas. Here we report the case of a 48-year-old man with a typical carcinoid tumour of the nasopharynx and sphenoid sinus. This is a very rare diagnosis, and only a few cases of a typical carcinoid in this region have been described in the literature.

[Influence of chemotherapy regimen on antioxidant level in patients with locally-advanced tumors of the maxilla, nasal and paranasal sinuses].

The study dealt with effect of chemoradiotherapy on the oxidant/antioxidant system in 57 patients with locally-advanced tumors (stage III-IV) of the maxilla, nasal and paranasal sinuses. Therapy modalities ranged from systemic chemoradiotherapy (22), intraarterial chemoradiotherapy + UHF-hyperthermia (20) and intraarterial chemotherapy + radiotherapy (15). The most frequent regimen of chemotherapy involved cisplatin 15 mg/ m2, total dose of 100 mg; fluorouracil 600 mg/m2, total dose of 2,000-3,000 mg, and doxorubicin 15 mg/m2, total dose of 40-60 mg. As far as telegammatherapy is concerned, all patients received STD of 3 Gy and TTD of 40-60 Gy. Unlike systemic chemoradiotherapy, continuous intraarterial chemoradiotherapy with UHF-hyperthermia or without it was followed by lower incidence of enhanced oxidative reaction response and tumor-related endotoxicosis.

Olfactory neuroblastoma causing ectopic ACTH syndrome.

A 39-year-old woman who presented with typical Cushingoid appearance (moon facies, central obesity, purpura) was admitted to our hospital because of pulmonary infection. She was found to have hypertension, severe hypokalemia, and metabolic alkalosis. Endocrine data revealed elevated plasma levels of ACTH and cortisol with lack of circadian rhythm, non-suppressibility to high-dose dexamethasone, and hyperresponsiveness to CRH stimulation. Although no pituitary mass was detected by MRI of the brain, inferior petrosal sinus sampling showed a step-up of central to peripheral ACTH levels; these data are consistent with the diagnosis of Cushing's disease. She was successfully treated with metyrapone to control hypercortisolemia. Ten months later, a mass was detected in the ethmoid sinus, which was surgically removed. After resection of the ethmoid sinus tumor, her Cushingoid features and hypercortisolemia disappeared, but recurred after enlargement of a second mass in the maxillary sinus. After resection of the maxillary sinus tumor, her hypercortisolemia subsided. Histologically, the tumor tissues from both the ethmoid and maxillary sinus were identical and consistent with the diagnosis of olfactory neuroblastoma. Immunohistochemically, the immunoreactivities of ACTH and POMC were positive in the cytoplasm of tumor cells, and immunoreactive ACTH was demonstrated in both tumor tissues. Thus, this is the second rare case with ectopic ACTH syndrome caused by olfactory neuroblastoma thus far reported.

Clinical value of serum squamous cell carcinoma antigen in the management of sinonasal inverted papilloma.

BACKGROUND: Although sinonasal inverted papilloma (IP) is a rare benign tumor, it has a tendency to recur and is sometimes associated with squamous cell carcinoma (SCC). Therefore, postoperative long-term follow-up of these patients is recommended. We previously reported that serum SCC antigen might be a useful tumor marker for sinonasal IP. In this study, we investigated whether serum SCC antigen level has a correlation with disease status and is useful in the early detection of recurrent disease. METHODS: Blood samples for the analysis of serum SCC antigen were taken from 28 IP patients before and after surgical treatment. RESULTS: Twenty-five (89%) of 28 cases showed evaluated serum SCC antigen levels above the upper limit. This marker level decreased in all cases after surgical resection. Four of these patients had a recurrence. None of the patients with recurrent tumor showed symptoms at the time of detection of their recurrent tumor, and recurrence was discovered from elevated levels of SCC antigen. CONCLUSIONS: Serum SCC antigen level has a correlation with disease status of IP and has a potential to serve as a useful tool for monitoring the course of disease. SCC antigen is a reliable tumor marker in the management of sinonasal IPs.

Serum squamous cell carcinoma antigen is a useful biologic marker in patients with inverted papillomas of the sinonasal tract.

BACKGROUND: Inverted papilloma (IP) is a frequent benign sinonasal tumor that is characterized histologically by squamous metaplasia, epithelial acanthosis, and hyperplasia of the nasal epithelium. Because of its high recurrence rate and malignant transformation potential, careful long-term follow up is necessary. METHODS: The purpose of the current report was to study the expression of squamous cell carcinoma (SCC) antigen in sinonasal IPs and to evaluate the usefulness of SCC antigen as a biologic marker for the follow-up of patients with sinonasal IP. The expression of SCCA1 in three sinonasal IP cases, three sinonasal SCC cases, and cases of normal nasal epithelium were examined by Western blot analysis, and the SCCA1 expression pattern in 31 IP specimens and 4 carcinoma in IP specimens were evaluated immunohistochemically. The serum levels of SCC antigen in 11 patients with sinonasal IP also were analyzed. RESULTS: SCCA1 was overexpressed in all three sinonasal IP tissues compared with sinonasal SCC tissues or normal nasal epithelium. SCCA1 cytoplasmic immunoreactivity was detected in the suprabasal epidermal keratinocytes of all 31 sinonasal IP cases. In the four carcinoma in IP specimens, SCCA1 expression in the papillomatous lesion was more intense than in the cancerous lesion. The serum SCC antigen level was high in 10 of 11 patients with IP (91%) and significantly decreased after surgical resection of the tumors. CONCLUSIONS: The results of the current study indicate that SCCA1 frequently is overexpressed and may play a biologic role in the development of sinonasal IPs. Serum SCC antigen may be a useful biologic marker in patients with sinonasal IP.

Concomitant infusion cisplatin and hyperfractionated radiotherapy for locally advanced nasopharyngeal and paranasal sinus tumors.

PURPOSE: This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy. METHODS AND MATERIALS: From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m2/24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation. RESULTS: Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included intense erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14%) developed confluent mucositis. Hematologically, one patient developed neutropenia (1800 WBC/mm3) and one developed thrombocytopenia (38,000/mm3). A rising creatinine was observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m2/day dose of infusional cisplatin. In all three of these cases, the creatinine slowly returned to normal over a 6-month period. Hormonal evaluations were performed in three patients and all were within normal ranges. There was no evidence of neck fibrosis or trismus. One patient with gross recurrent disease of the orbit developed blindness of the involved eye due to corneal opacification. The orbital area had been reirradiated in this patient. CONCLUSIONS: Concomitant infusion cisplatinum with hyperfractionated radiation improved tumor control, but did not increase normal tissue injury. Acute reactions were minimized by splitting the treatment with a 1- to 2-week break after each 2 weeks of radiation treatment. Late complications were not increased by using a hyperfractionated radiation regimen. The local failure rate was only 18% (3 of 17 patients), but the distant failure rate was 35% (6 patients). Further investigation is needed to prove if adjuvant chemotherapy after concomitant chemoradiation improves survival by decreasing the distant failure in such advanced cases.

Sphenoid sinus localization of multiple myeloma revealing evolution from benign gammopathy.

BACKGROUND: Plasma-cell neoplasms of the head and neck include extramedullary plasmacytoma and solitary plasmocytoma of bone or may represent a local manifestation of multiple myeloma. Involvement of sphenoid sinus has been rarely reported in multiple myeloma. METHODS: We present the case of a 77-year-old man with a 3-year-history of benign monoclonal IgG-lambda gammopathy who developed left sixth-nerve palsy and malaise. RESULTS: Computed tomography scan and magnetic resonance imaging scan disclosed a large soft-tissue mass of the sphenoid sinus with bone destruction. Sphenoid sinus biopsy revealed an IgG monoclonal plasma cell neoplasm. Diagnosis of multiple myeloma stage IA was then established. CONCLUSIONS: Diagnosis of plasma-cell neoplasm should be considered in sphenoid sinus tumors and depends upon histologic examination. This case enlightens the relationships between monoclonal benign gammopathy and plasma-cell neoplasms of the head and neck which constitute a continuum of B-cell lymphoproliferative disorders.

[The concentration of ferritin in blood serum of patients with neoplasms of the larynx and the maxillary-ethmoidal complex]. / Stezenie ferrytyny w surowicy krwi u chorych na nowotwory zlosliwe krtani lub masywu szczekowo-sitowego.

The increased level of ferritin is known as a nonspecific marker of inflammatory processes and neoplasms. A purpose of the article was to indicate concentration of ferritin in blood serum before treatment of 33 patients with cancer of larynx and 16 patients with malignant neoplasms of maxillo-ethmoid complex. The patients with cancer of larynx were characterized by significantly high level of ferritin in comparison to patients with malignant neoplasms of maxillo-ethmoid complex (p < 0.05) and to healthy people (p < 0.05) (respectively 241.9 +/- 154.9; 106.9 +/- 45.4 and 125.0 +/- 30.4 ng/ml). Contrary to patients with cancer of larynx patients with malignant neoplasms of maxillo-ethmoid complex did not differ in significant level of ferritin from healthy people. The concentration of hemoglobin in blood in both groups of patients was similar and was characteristically lower than values obtained in healthy people. The results achieved suggest that indicating of ferritin can be helpful while making a differentiation between cancer of larynx and malignant neoplasms of maxillo-ethmoid complex.