The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: Refinements in diagnostic criteria and impact of multimodal treatments on survival.

OBJECTIVES: To provide a comprehensive review of the clinical and histopathological features of olfactory neuroblastoma (ONB) and other sinonasal neuroendocrine neoplasms (NENs), in order to refine diagnostic criteria, analyze treatment outcomes, and identify prognostic factors. METHODS: Data from an Italian multi-institutional database were analyzed. Patients were treated surgically via a minimally-invasive endoscopic approach followed by adjuvant radiotherapy or radiochemotherapy. Neoadjuvant cisplatin/etoposide chemotherapy was administered in cases of poorly-differentiated tumors. A centralized pathology review was performed in all cases. Patients were prospectively observed for survival. Overall (OS) and Disease-free survival (DFS) estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Statistically significant variables were entered in a multivariate Cox regression model. RESULTS: 98 patients with a median follow-up of 53months were included. Morphology review and the incorporation of cytokeratin 8/18 in the immunohistochemical panel modified the final diagnosis in 8/98 (8.2%) cases. The neoplasms were ultimately classified into four groups with different immunohistochemical profiles and clinical behaviors: ONB in 67 cases (5-year-OS, 91.6%); NEC (poorly-differentiated neuroendocrine carcinoma) in 22 cases (5-year-OS, 42.6%); MiNEN (mixed neuroendocrine/non-neuroendocrine neoplasm) in five cases (5-year-OS, 0%,0/5 cases); and NET (well-differentiated neuroendocrine tumor) in four cases (5-year-OS, 50%, 2/4 cases). Hyams grade and Ki67 index were independent prognostic factors for ONB. Neoadjuvant chemotherapy appeared to be associated with improved OS and DFS for NEC, independent of other clinicopathological variables. CONCLUSIONS: Induction chemotherapy improves survival outcomes in patients affected by poorly-differentiated tumors. Recent advances in histopathological diagnosis, including CK8/18 staining, allow to plan the most appropriate range of multimodal treatments.

Incidental 18F-FDG PET/CT bilateral breast uptake due to carcinoma.

We report a case of 71-year-old female patient, previously treated with chemotherapy and surgical resection of sigmoid tract of the large bowel for adenocarcinoma (pT3N1M0), who underwent a 18F-FDG PET/CT for a suspicious hepatic lesion detected at CT scan during follow-up. 18F-FDG PET/CT showed no abnormal uptake in the liver both at 60 minutes and 120 minutes after injection but revealed a pathological uptake in two breast nodules, (one localized in upper-internal-quadrant of the right breast and the other in the upper-external-quadrant of the left breast). The patient underwent breast MRI, which confirmed the suspicious nature of both lesions; subsequently she underwent a trucut biopsy of both lesions witch demonstrated a bilateral localization of papillary carcinoma (both lesion were classified as pT1c). The patient underwent bilateral mastectomy and the final biopsy confirmed the presence of breast cancer, while bilateral sentinel nodes biopsy showed no lymph-nodes metastases.

Sinonasal mucosal melanoma: A 12-year experience of 58 cases.

BACKGROUND: Sinonasal mucosal melanoma is a rare malignancy with poor prognosis. METHODS: Patients with sinonasal malignant melanoma who underwent surgery by different approaches were included in this study. Overall survival (OS) and event-free survival were calculated, and statistically significant variables by univariate analysis were entered in a multivariate Cox regression model. RESULTS: Pathological staging was pT3, pT4a, and pT4b in 30 cases (51.7%), 17 cases (29.3%), and 11 cases (19.0%). At 3 and 5 years, OS was 43.5% and 29% and event-free survival was 23.6% and 12.4%, respectively. At univariate analysis, OS was significantly influenced by male sex, advanced pT classification, positive margins, and surgical approach; event-free survival was affected by positive margins. At multivariate analysis, the risk of death was independently associated with male sex (hazard ratio [HR] = 2.27; p = .04) and positive margins (HR = 2.32; p = .03). CONCLUSION: Male sex and positive margins were negative prognostic factors. Endoscopic resection did not show an increased risk of death compared with more extensive surgical approaches. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1737-E1745, 2016.

Giant hypervascular lesion of the sinonasal tract invading the anterior skull base and orbit: a puzzling case.

The sinonasal tract may be involved in a wide variety of hypervascular lesions, either benign or malignant, and differential diagnosis may be challenging. We present the case of a 26-year-old man with an aggressive ethmoid hypervascular mass invading the anterior skull base and orbit. Because of massive intraoperative bleeding and difficult dissection of the lesion from the periorbita, the planned cranioendoscopic approach had to be converted into a standard craniofacial resection by a combined Lynch and coronal incision. The definitive diagnosis was consistent with lobular capillary hemangioma associated with intravascular papillary endothelial hyperplasia. Two years after surgery, the patient is free of disease. Lobular capillary hemangioma is a hypervascular lesion that may involve the sinonasal tract. The case presented herein is exceptional, both in the presentation and in the difficulties encountered in diagnosis and treatment, because of the concurrence of lobular capillary hemangioma and intravascular papillary endothelial hyperplasia.

Amplification and overexpression of HER2/neu gene and HER2/neu protein in salivary duct carcinoma of the parotid gland.

OBJECTIVES: To detect amplification of the HER2/neu gene by means of fluorescence in situ hybridization (FISH) in a series of 13 salivary duct carcinomas (SDCs) and to compare the results with immunohistochemical (IHC) assessment of HER2/neu protein expression. DESIGN: Retrospective analysis. SETTING: Department of Pathology, University of Brescia. PATIENTS: We studied 13 cases of SDC diagnosed between January 1, 1997, and June 30, 2004, all arising from the parotid gland. Twelve patients were treated with surgery and radiotherapy, and 1 patient received only palliative radiotherapy. Seven patients died of disease, 3 patients were alive with disease, and 3 were free of disease. MAIN OUTCOME MEASURES: HER2/neu protein expression and HER2/neu gene amplification detected by means of IHC assessment and FISH, respectively. RESULTS: With IHC assessment, 10 cases showed overexpression (grade 3+) of HER2/neu protein, whereas 3 cases were negative for this protein (grade 0/1+). Using FISH, amplification of the HER2/neu gene was found in 8 of the 10 grade 3+ cases, whereas none of the cases negative for the protein according to IHC assessment had amplification of the gene. Because of the small number of patients, it was not possible to statistically correlate HER2/neu protein expression or HER2/neu gene amplification and survival. CONCLUSION: Our data demonstrate that HER2/neu protein is frequently overexpressed in SDC, and in contrast to previous reports, overexpression of the protein is associated in most cases with HER2/neu gene amplification.

Prognostic factors in well-differentiated thyroid carcinoma in patients treated and followed in the same institution.

AIM: To test the prognostic significant of clinicopathologic factors in patients affected by well-differentiated thyroid carcinoma (WDTC). METHODS: A retrospective review of patients treated for WDTC (thyroidectomy and a radioactive iodine (1131) thyroid ablation) at our Institute with a minimum of 10 years of follow-up was carried out. The unfavourable prognosis at the end of the follow-up was defined as persistence/recurrence of WDTC or death due to the cancer. RESULTS: 234 patients (162 female, 72 male), mean age of 47.6 +/- 166 years, were included in this study (mean follow-up 158.4 +/- 34.8 months): 78 (33.4%) subjects had persistence/recurrence of neoplasia while 5 (2.1%) died for cancer. The multivariate regression showed that prognostic factors were old age, size of cancer, detectable thyroglonulin levels six months after metabolic ablation, and DeGroot staging system. DISCUSSION: Our mortality rate is lower (2.1%) than reported in literature (10%): this could be explained by the different pathological classification and treatment. The mortality rate appears higher in patients treated with emitiroidectomy and TSH suppressive therapy than in those with total thyroidectomy and I131 ablation. Even if we have chosen an "aggressive" therapy and our mortality rate is lower, one third of patients have persistence/recurrence of cancer: it seems that tumour recurrence rate better reflects clinical problems related to cancer. CONCLUSION: WDTC has with a good disease-specific survival but a significant recurrence rate. The most important predictors are the old age and the size of lesion. We suggest a radical surgery followed by radiometabolic ablation in all patients with WDTC.

Massive apoptosis erodes nasal mucosa of cocaine abusers.

BACKGROUND: A threatening occurrence in some cocaine abusers is the progressive destruction of nasal structures (cocaine-induced midline destructive lesions [CIMDL]) that may end in a highly severe disease. METHODS: Thirty patients with CIMDL, 10 healthy patients, 10 patients affected by nasal polyposis, and 10 patients affected by Wegener granulomatosis were observed. Biopsy specimens of nasal mucosa were analyzed by immunohistochemistry for caspases-3, -9 and -8 and by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxygenin nick end labeling (TUNEL) method. The time and concentration-dependent effects of cocaine in vitro were studied in HaCat cells by TUNEL and Western blotting. RESULTS: All CIMDL biopsy specimens showed abundant caspase-3 and caspase-9 expression but no caspase-8 positive cells. No obvious expression of any caspases was detected in biopsy specimens from healthy subjects or in patients affected by nasal polyposis or Wegener granulomatosis. In HaCat cells cellular changes were observed, which confirmed induction of massive apoptotic events. The rate of apoptosis in HaCat cells was dependent on the concentration of cocaine. After 1 hour, 2.5, 5, and 10 mM of cocaine induced 16, 45, and 84% of apoptotic figures, respectively, while 6 hours of exposure increased apoptosis to 25, 54, and 94% at the same concentrations. Caspase expression and activation in HaCat cells treated with 100 microM and 1 mM of cocaine for 1 hour were confirmed by Western blotting. CONCLUSION: Cultured epithelial cells show both time- and dose-dependent increases in apoptosis and cellular damage on cocaine treatment. We suggest that some abusers trigger CIMDL by abnormally boosting apoptosis within nasal epithelial cells. Cocaine abusers with higher apoptotic rates may predict whether they will eventually develop CIMDL.

Oncocytic carcinoma of the maxillary sinus: a rare neoplasm.

Oncocytic neoplasms are tumors composed of oncocytes (i.e., epithelial cells with a large cytoplasm that is rich in mitochondria). Most cases are benign and originate from the major salivary glands, while the minor salivary glands are rarely involved. Occurrence of oncocytic carcinoma (or malignant oncocytoma) within the sinonasal tract is an unusual event. We report a rare case of maxillary sinus oncocytic carcinoma occurring in a 45-year-old male. Biopsy was consistent with an unspecified salivary gland neoplasm. The patient underwent total maxillectomy through a lateral rhinotomic approach; hard palate reconstruction with temporal myofascial flap was performed. Definitive histology was consistent with oncocytic carcinoma. Due to the local extension of the lesion, postoperative radiotherapy (60 Gy) was delivered. Three years after surgery, the patient is free from disease. A brief analysis of the literature was also accomplished in order to discuss treatment options and prognosis of this unusual neoplasm.

Sinonasal osteocartilaginous necrosis in cocaine abusers: experience in 25 patients.

BACKGROUND: Cocaine-induced lesions may cause extensive destruction of the osteocartilaginous structures of the nose, sinuses, and palate that mimics the clinical picture of other diseases. METHODS: From January 1991 to September 2001 25 patients with cocaine-induced midline destructive lesions were observed at the Department of Otorhinolaryngology of the University of Brescia. The diagnosis was based on physical and endoscopic evaluation, routine blood and urine analysis, radiological findings, and repeated biopsies of the nasal mucosa. Serum was analyzed by the antineutrophilic cytoplasmic antibody (ANCA) test using indirect immunofluorescence and by enzyme-linked immunosorbent assay for antibodies against proteinase 3 and myeloperoxidase. RESULTS: Septal perforation was present in all 25 patients, 16 of which (68%) also had partial destruction of the inferior turbinate. Hard palate reabsorption was observed in only six patients (24%); in two of these patients, the lesion also extended to the soft palate. Fourteen patients (56%) were positive by the immunofluorescence test (nine patients had a P-ANCA and five patients a C-ANCA pattern). Four patients (16%) with the P-ANCA pattern and all patients with the C-ANCA pattern also tested positive for anti-proteinase 3 antibodies. CONCLUSION: Any sinonasal inflammation involving the midline that persists or remains refractory to treatment may be the first manifestation of potentially lethal drug addiction. Cocaine abuse should be considered in the differential diagnosis of destructive lesions of the nasal cavity even in the presence of a positive ANCA test.